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Yasuko Iwakiri, PhD

Professor of Medicine (Digestive Diseases)

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Yasuko Iwakiri, PhD

Office Location

Mailing Address

  • Yale School of Medicine

    Department of Medicine (Digestive Diseases), PO Box 208019

    New Haven, CT 06520-8019

    United States

Iwakiri Lab
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Research Summary

The central focus of my research is the study of liver fibrosis and portal hypertension. Both are major subjects in the study of liver disease. My laboratory also investigates the role of vascular biology in liver disease pathogenesis. Although the pathology of the liver has examined cellular components and functions of the liver, the contribution of the vasculature both inside and outside the liver and related hemodynamic changes have not been well investigated. This is the uniqueness of my research and originated from my study of portal hypertension, which represents a liver and vascular disease.

Extensive Research Description

Vascular biology of the liver:

My lab has been committed to working on the lymphatic system in the liver, which is a very unexplored area in the study of liver biology (Chung & Iwakiri, CMH, 2013; Iwakiri, Hepatology, 2016; Tanaka & Iwakiri, CMGH, 2016).

Liver fibrosis:

  1. We investigate the role of each major liver cell type in fibrogenesis with a particular interest in hepatic stellate cells (HSC), a cell type that has the most direct impact on the development of fibrosis. We have determined that a protein called Reticulon 4B (a.k.a., Nogo-B) increases fibrosis by promoting collagen production by HSCs (Zhang et al., Hepatology, 2011) and protecting HSCs from apoptosis (Tashiro et al., Am J Pathol, 2013).
  2. In collaboration with Dr. Mark Saltzman (Yale University), we have explored the therapeutic potential of targeting Reticulon 4B in HSCs for liver fibrosis by delivering siRNA encapsulated in nanoparticles. While nanoparticles have been considered an important tool for delivery of drugs and the liver has been known to retain nanoparticles, their cellular distribution in the liver was not clearly understood. We conducted extensive analyses of liver cell uptake of nanoparticles and demonstrated their cellular distribution in vivo for the first time (Park et al., Nanomedicine, 2016). This study is significant since the effectiveness and safety of medical application of nanoparticles for liver therapy depends on their specific delivery to targeted cell populations.

Kupffer cells/macrophages in the pathogenesis of alcohol-induced liver disease:

Alcohol abuse causes liver disease, whose spectrum includes alcoholic fatty liver, alcoholic hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma in a progressive manner. Early intervention may prevent progression to cirrhosis and hepatocellular carcinoma, but effective treatments are limited due to our incomplete understanding of the molecular and cellular mechanisms of alcohol-induced liver injury. My lab studies the mechanism of alcohol-induced liver injury, in which Kupffer cells (liver resident macrophages) have a pivotal role. We also explore therapeutic potential of nanoparticle delivery to Kupffer cells for the treatment of alcoholic liver disease.

Coauthors

Research Interests

Fibrosis; Hypertension, Portal; Kupffer Cells; Liver Regeneration; Pancreatitis; Splenomegaly; Vascular Diseases; Lymphangiogenesis; Endothelial Cells

Public Health Interests

Cancer; Cardiovascular Diseases

Research Image

Immune cell infiltration to the portal tract of the liver

Macrophages (green) and T-cells (red) are infiltrated to the portal tract area of the liver in response to the induction of portal hypertension in rats. These cells play roles for portal tract fibrosis in the liver.

Selected Publications

  • Effect of red palm olein on bone tissue fatty acid composition and histomorphometric parametersWatkins, B.A., Li, Y., Rogers, L.L., Hoffmann, W.E., Iwakiri, Y., Allen, K.G.D., and Seifert, M.F. Nutrition Research. 2001;21(1-2):199-213.
  • Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages.Iwakiri Y, Sampson DA, Allen KG. Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages. Prostaglandins, Leukotrienes, And Essential Fatty Acids 2002, 67: 435-43. PMID: 12468265, DOI: 10.1054/plef.2002.0454.
  • Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension.Iwakiri Y, Tsai MH, McCabe TJ, Gratton JP, Fulton D, Groszmann RJ, Sessa WC. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. American Journal Of Physiology. Heart And Circulatory Physiology 2002, 282: H2084-90. PMID: 12003815, DOI: 10.1152/ajpheart.00675.2001.
  • Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension.Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2002, 283: G1074-81. PMID: 12381520, DOI: 10.1152/ajpgi.00145.2002.
  • Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats.Tsai MH, Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003, 125: 1452-61. PMID: 14598261, DOI: 10.1016/j.gastro.2003.07.014.
  • Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice.Gratton JP, Lin MI, Yu J, Weiss ED, Jiang ZL, Fairchild TA, Iwakiri Y, Groszmann R, Claffey KP, Cheng YC, Sessa WC. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2003, 4: 31-9. PMID: 12892711, DOI: 10.1016/s1535-6108(03)00168-5.
  • A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats.Loureiro-Silva MR, Cadelina GW, Iwakiri Y, Groszmann RJ. A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. Journal Of Hepatology 2003, 39: 940-6. PMID: 14642609, DOI: 10.1016/j.jhep.2003.09.018.
  • Targeting of endothelial nitric-oxide synthase to the cytoplasmic face of the Golgi complex or plasma membrane regulates Akt- versus calcium-dependent mechanisms for nitric oxide release.Fulton D, Babbitt R, Zoellner S, Fontana J, Acevedo L, McCabe TJ, Iwakiri Y, Sessa WC. Targeting of endothelial nitric-oxide synthase to the cytoplasmic face of the Golgi complex or plasma membrane regulates Akt- versus calcium-dependent mechanisms for nitric oxide release. The Journal Of Biological Chemistry 2004, 279: 30349-57. PMID: 15136572, DOI: 10.1074/jbc.M402155200.
  • Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis.Ackah E, Yu J, Zoellner S, Iwakiri Y, Skurk C, Shibata R, Ouchi N, Easton RM, Galasso G, Birnbaum MJ, Walsh K, Sessa WC. Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis. The Journal Of Clinical Investigation 2005, 115: 2119-27. PMID: 16075056, PMCID: PMC1180542, DOI: 10.1172/JCI24726.
  • Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking.Iwakiri Y, Satoh A, Chatterjee S, Toomre DK, Chalouni CM, Fulton D, Groszmann RJ, Shah VH, Sessa WC. Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 19777-82. PMID: 17170139, PMCID: PMC1750883, DOI: 10.1073/pnas.0605907103.
  • Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers.Loureiro-Silva MR, Iwakiri Y, Abraldes JG, Haq O, Groszmann RJ. Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. Journal Of Hepatology 2006, 44: 886-93. PMID: 16545481, DOI: 10.1016/j.jhep.2006.01.032.
  • The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule.Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology (Baltimore, Md.) 2006, 43: S121-31. PMID: 16447289, DOI: 10.1002/hep.20993.
  • Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state.Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2006, 290: G980-7. PMID: 16603731, DOI: 10.1152/ajpgi.00336.2005.
  • Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease.Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WC. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metabolism 2007, 6: 446-57. PMID: 18054314, PMCID: PMC3621848, DOI: 10.1016/j.cmet.2007.10.007.
  • The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension.Iwakiri Y. The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension. Journal Of Clinical Gastroenterology 2007, 41 Suppl 3: S288-94. PMID: 17975478, DOI: 10.1097/MCG.0b013e3181468b4c.
  • Increased neuronal nitric oxide synthase interaction with soluble guanylate cyclase contributes to the splanchnic arterial vasodilation in portal hypertensive rats.Kwon SY, Groszmann RJ, Iwakiri Y. Increased neuronal nitric oxide synthase interaction with soluble guanylate cyclase contributes to the splanchnic arterial vasodilation in portal hypertensive rats. Hepatology Research : The Official Journal Of The Japan Society Of Hepatology 2007, 37: 58-67. PMID: 17300699, DOI: 10.1111/j.1872-034X.2007.00005.x.
  • Decreased intrahepatic response to alpha(1)-adrenergic agonists in lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function.Lee CH, Loureiro-Silva MR, Abraldes JG, Iwakiri Y, Haq O, Groszmann RJ. Decreased intrahepatic response to alpha(1)-adrenergic agonists in lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function. Journal Of Gastroenterology And Hepatology 2007, 22: 893-900. PMID: 17498219, DOI: 10.1111/j.1440-1746.2007.04922.x.
  • Vascular endothelial dysfunction in cirrhosis.Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. Journal Of Hepatology 2007, 46: 927-34. PMID: 17391799, DOI: 10.1016/j.jhep.2007.02.006.
  • Vascular biology and pathobiology of the liver: Report of a single-topic symposium.Iwakiri Y, Grisham M, Shah V. Vascular biology and pathobiology of the liver: Report of a single-topic symposium. Hepatology (Baltimore, Md.) 2008, 47: 1754-63. PMID: 18393322, PMCID: PMC2724750, DOI: 10.1002/hep.22203.
  • The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma.Shibao K, Fiedler MJ, Nagata J, Minagawa N, Hirata K, Nakayama Y, Iwakiri Y, Nathanson MH, Yamaguchi K. The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma. Cell Calcium 2010, 48: 315-23. PMID: 21075448, PMCID: PMC3572849, DOI: 10.1016/j.ceca.2010.09.005.
  • Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis.Zhang D, Utsumi T, Huang HC, Gao L, Sangwung P, Chung C, Shibao K, Okamoto K, Yamaguchi K, Groszmann RJ, Jozsef L, Hao Z, Sessa WC, Iwakiri Y. Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis. Hepatology (Baltimore, Md.) 2011, 53: 1306-15. PMID: 21480333, PMCID: PMC3667398, DOI: 10.1002/hep.24200.
  • S-nitrosylation of proteins: a new insight into endothelial cell function regulated by eNOS-derived NO.Iwakiri Y. S-nitrosylation of proteins: a new insight into endothelial cell function regulated by eNOS-derived NO. Nitric Oxide : Biology And Chemistry / Official Journal Of The Nitric Oxide Society 2011, 25: 95-101. PMID: 21554971, PMCID: PMC3152628, DOI: 10.1016/j.niox.2011.04.014.
  • Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.Schmitz JC, Protiva P, Gattu AK, Utsumi T, Iwakiri Y, Neto AG, Quinn M, Cornwell ML, Fitchev P, Lugea A, Crawford SE, Chung C. Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1. The American Journal Of Pathology 2011, 179: 2990-9. PMID: 21964188, PMCID: PMC3260804, DOI: 10.1016/j.ajpath.2011.08.009.
  • A role of miR-33 for cell cycle progression and cell proliferation.Iwakiri Y. A role of miR-33 for cell cycle progression and cell proliferation. Cell Cycle (Georgetown, Tex.) 2012, 11: 1057-8. PMID: 22395363, DOI: 10.4161/cc.11.6.19744.
  • Proteomic identification of S-nitrosylated Golgi proteins: new insights into endothelial cell regulation by eNOS-derived NO.Sangwung P, Greco TM, Wang Y, Ischiropoulos H, Sessa WC, Iwakiri Y. Proteomic identification of S-nitrosylated Golgi proteins: new insights into endothelial cell regulation by eNOS-derived NO. PloS One 2012, 7: e31564. PMID: 22363674, PMCID: PMC3283662, DOI: 10.1371/journal.pone.0031564.
  • Activated hepatic stellate cells: negative regulators of hepatocyte proliferation in liver diseases.Chung C, Iwakiri Y. Activated hepatic stellate cells: negative regulators of hepatocyte proliferation in liver diseases. Hepatology (Baltimore, Md.) 2012, 56: 389-91. PMID: 22876366, PMCID: PMC3666938, DOI: 10.1002/hep.25761.
  • Endothelial dysfunction in the regulation of cirrhosis and portal hypertension.Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver International : Official Journal Of The International Association For The Study Of The Liver 2012, 32: 199-213. PMID: 21745318, PMCID: PMC3676636, DOI: 10.1111/j.1478-3231.2011.02579.x.
  • Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure.Huang HC, Haq O, Utsumi T, Sethasine S, Abraldes JG, Groszmann RJ, Iwakiri Y. Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure. Journal Of Cellular And Molecular Medicine 2012, 16: 1125-33. PMID: 21801303, PMCID: PMC3213314, DOI: 10.1111/j.1582-4934.2011.01399.x.
  • Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity.Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan MJ, Chairoungdua A, Lu J, Adams BD, Sikora E, Nazimek K, Marquez S, Kleinstein SH, Sangwung P, Iwakiri Y, Delgato E, Redegeld F, Blokhuis BR, Wojcikowski J, Daniel AW, Groot Kormelink T, Askenase PW. Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. The Journal Of Allergy And Clinical Immunology 2013, 132: 170-81. PMID: 23727037, PMCID: PMC4176620, DOI: 10.1016/j.jaci.2013.04.048.
  • The lymphatic vascular system in liver diseases: its role in ascites formation.Chung C, Iwakiri Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clinical And Molecular Hepatology 2013, 19: 99-104. PMID: 23837133, PMCID: PMC3701854, DOI: 10.3350/cmh.2013.19.2.99.
  • Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content.Gattu AK, Swenson ES, Iwakiri Y, Samuel VT, Troiano N, Berry R, Church CD, Rodeheffer MS, Carpenter TO, Chung C. Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2013, 27: 4384-94. PMID: 23887690, PMCID: PMC3804749, DOI: 10.1096/fj.13-232900.
  • eNOS-derived nitric oxide regulates endothelial barrier function through VE-cadherin and Rho GTPases.Di Lorenzo A, Lin MI, Murata T, Landskroner-Eiger S, Schleicher M, Kothiya M, Iwakiri Y, Yu J, Huang PL, Sessa WC. eNOS-derived nitric oxide regulates endothelial barrier function through VE-cadherin and Rho GTPases. Journal Of Cell Science 2013, 126: 5541-52. PMID: 24046447, PMCID: PMC3860306, DOI: 10.1242/jcs.115972.
  • Absence of Nogo-B (reticulon 4B) facilitates hepatic stellate cell apoptosis and diminishes hepatic fibrosis in mice.Tashiro K, Satoh A, Utsumi T, Chung C, Iwakiri Y. Absence of Nogo-B (reticulon 4B) facilitates hepatic stellate cell apoptosis and diminishes hepatic fibrosis in mice. The American Journal Of Pathology 2013, 182: 786-95. PMID: 23313137, PMCID: PMC3586693, DOI: 10.1016/j.ajpath.2012.11.032.
  • Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice.Gao L, Utsumi T, Tashiro K, Liu B, Zhang D, Swenson ES, Iwakiri Y. Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice. Hepatology (Baltimore, Md.) 2013, 57: 1992-2003. PMID: 23299899, PMCID: PMC3628958, DOI: 10.1002/hep.26235.
  • Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions.Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions. Journal Of Hepatology 2014, 61: 912-24. PMID: 24911462, PMCID: PMC4346093, DOI: 10.1016/j.jhep.2014.05.047.
  • Pigment epithelium-derived factor (PEDF) suppresses IL-1β-mediated c-Jun N-terminal kinase (JNK) activation to improve hepatocyte insulin signaling.Gattu AK, Birkenfeld AL, Iwakiri Y, Jay S, Saltzman M, Doll J, Protiva P, Samuel VT, Crawford SE, Chung C. Pigment epithelium-derived factor (PEDF) suppresses IL-1β-mediated c-Jun N-terminal kinase (JNK) activation to improve hepatocyte insulin signaling. Endocrinology 2014, 155: 1373-85. PMID: 24456163, PMCID: PMC5393334, DOI: 10.1210/en.2013-1785.
  • Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry.Jozsef L, Tashiro K, Kuo A, Park EJ, Skoura A, Albinsson S, Rivera-Molina F, Harrison KD, Iwakiri Y, Toomre D, Sessa WC. Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry. The Journal Of Biological Chemistry 2014, 289: 9380-95. PMID: 24558039, PMCID: PMC3969502, DOI: 10.1074/jbc.M114.548602.
  • Pathophysiology of portal hypertension.Iwakiri Y. Pathophysiology of portal hypertension. Clinics In Liver Disease 2014, 18: 281-91. PMID: 24679494, PMCID: PMC3971388, DOI: 10.1016/j.cld.2013.12.001.
  • Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.Iwakiri Y. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase. Clinical And Molecular Hepatology 2015, 21: 319-25. PMID: 26770919, PMCID: PMC4712158, DOI: 10.3350/cmh.2015.21.4.319.
  • Hepatic congestion leads to fibrosis: findings in a newly developed murine model.Hidaka H, Iwakiri Y. Hepatic congestion leads to fibrosis: findings in a newly developed murine model. Hepatology (Baltimore, Md.) 2015, 61: 428-30. PMID: 25283276, PMCID: PMC4303496, DOI: 10.1002/hep.27550.
  • Development of small diameter nanofiber tissue engineered arterial grafts.Kurobe H, Maxfield MW, Tara S, Rocco KA, Bagi PS, Yi T, Udelsman B, Zhuang ZW, Cleary M, Iwakiri Y, Breuer CK, Shinoka T. Development of small diameter nanofiber tissue engineered arterial grafts. PloS One 2015, 10: e0120328. PMID: 25830942, PMCID: PMC4382213, DOI: 10.1371/journal.pone.0120328.
  • Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension.Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed Fel Z, Davies N, Sharma V, Iwakiri Y, Jalan R. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. Journal Of Hepatology 2015, 62: 325-31. PMID: 25152204, PMCID: PMC4530584, DOI: 10.1016/j.jhep.2014.08.024.
  • Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver.Protiva P, Gong J, Sreekumar B, Torres R, Zhang X, Belinsky GS, Cornwell M, Crawford SE, Iwakiri Y, Chung C. Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver. Cellular And Molecular Gastroenterology And Hepatology 2015, 1: 535-549.e14. PMID: 26473164, PMCID: PMC4604042, DOI: 10.1016/j.jcmgh.2015.06.006.
  • Can hypersplenism secondary to portal hypertension be treated by non-selective beta blockers?Kim MY, Iwakiri Y. Can hypersplenism secondary to portal hypertension be treated by non-selective beta blockers? Hepatology International 2015, 9: 337-8. PMID: 25788189, PMCID: PMC5046185, DOI: 10.1007/s12072-014-9601-1.
  • Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a.Wang S, Song K, Srivastava R, Dong C, Go GW, Li N, Iwakiri Y, Mani A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2015, 29: 3436-45. PMID: 25917329, PMCID: PMC4511193, DOI: 10.1096/fj.15-271171.
  • Nitric oxide in liver diseases.Iwakiri Y, Kim MY. Nitric oxide in liver diseases. Trends In Pharmacological Sciences 2015, 36: 524-36. PMID: 26027855, PMCID: PMC4532625, DOI: 10.1016/j.tips.2015.05.001.
  • The lymphatic system: A new frontier in hepatology.Iwakiri Y. The lymphatic system: A new frontier in hepatology. Hepatology (Baltimore, Md.) 2016, 64: 706-7. PMID: 27228259, PMCID: PMC4992465, DOI: 10.1002/hep.28650.
  • The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis.Tanaka M, Iwakiri Y. The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis. Cellular And Molecular Gastroenterology And Hepatology 2016, 2: 733-749. PMID: 28105461, PMCID: PMC5240041, DOI: 10.1016/j.jcmgh.2016.09.002.
  • Cellular distribution of injected PLGA-nanoparticles in the liver.Park JK, Utsumi T, Seo YE, Deng Y, Satoh A, Saltzman WM, Iwakiri Y. Cellular distribution of injected PLGA-nanoparticles in the liver. Nanomedicine : Nanotechnology, Biology, And Medicine 2016, 12: 1365-74. PMID: 26961463, PMCID: PMC4889500, DOI: 10.1016/j.nano.2016.01.013.
  • Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis.Shao M, Tian T, Zhu X, Ming Y, Iwakiri Y, Ye S, Ye Q. Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis. Oncotarget 2017, 8: 66426-66437. PMID: 29029524, PMCID: PMC5630424, DOI: 10.18632/oncotarget.19815.
  • Corrigendum to "Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension" [J Hepatol 62 (2015) 325-331].Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed FEZ, Davies N, Sharma V, Iwakiri Y, Jalan R. Corrigendum to "Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension" [J Hepatol 62 (2015) 325-331]. Journal Of Hepatology 2017, 67: 1124. PMID: 28893453, DOI: 10.1016/j.jhep.2017.08.004.
  • Reply.Iwakiri Y. Reply. Hepatology (Baltimore, Md.) 2017, 65: 2134. PMID: 28195342, DOI: 10.1002/hep.29102.
  • Reply.Park JK, Iwakiri Y. Reply. Hepatology (Baltimore, Md.) 2017, 66: 1702-1703. PMID: 28745830, DOI: 10.1002/hep.29404.
  • Novel application and serial evaluation of tissue-engineered portal vein grafts in a murine model.Maxfield MW, Stacy MR, Kurobe H, Tara S, Yi T, Cleary MA, Zhuang ZW, Rodriguez-Davalos MI, Emre SH, Iwakiri Y, Shinoka T, Breuer CK. Novel application and serial evaluation of tissue-engineered portal vein grafts in a murine model. Regenerative Medicine 2017, 12: 929-938. PMID: 29215317, PMCID: PMC5827823, DOI: 10.2217/rme-2017-0021.
  • An endoplasmic reticulum protein, Nogo-B, facilitates alcoholic liver disease through regulation of kupffer cell polarization.Park JK, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo-B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology (Baltimore, Md.) 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.
  • Alcohol and calcium make a potent cocktail.Iwakiri Y, Nathanson MH. Alcohol and calcium make a potent cocktail. The Journal Of Physiology 2017, 595: 3109-3110. PMID: 28295353, PMCID: PMC5430223, DOI: 10.1113/JP274133.
  • Biology of portal hypertension.McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatology International 2018, 12: 11-23. PMID: 29075990, PMCID: PMC7090883, DOI: 10.1007/s12072-017-9826-x.
  • The portal hypertension syndrome: etiology, classification, relevance, and animal models.Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatology International 2018, 12: 1-10. PMID: 29064029, DOI: 10.1007/s12072-017-9827-9.
  • Is miR-21 a potent target for liver fibrosis?Lai S, Iwakiri Y. Is miR-21 a potent target for liver fibrosis? Hepatology (Baltimore, Md.) 2018, 67: 2082-2084. PMID: 29315674, PMCID: PMC5992001, DOI: 10.1002/hep.29774.
  • Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, Kinoshita R, Enoki Y, Imafuku T, Chuang VTG, Koga T, Fujiwara Y, Takeya M, Sonoda K, Wakayama T, Taguchi K, Ishima Y, Ishida T, Iwakiri Y, Tanaka M, Sasaki Y, Watanabe H, Otagiri M, Maruyama T. Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions. Drug Delivery 2018, 25: 1067-1077. PMID: 29688069, PMCID: PMC6058604, DOI: 10.1080/10717544.2018.1464083.
  • Lymphatics in the liver.Tanaka M, Iwakiri Y. Lymphatics in the liver. Current Opinion In Immunology 2018, 53: 137-142. PMID: 29772409, PMCID: PMC6986420, DOI: 10.1016/j.coi.2018.04.028.
  • Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats.Saruwatari J, Dong C, Utsumi T, Tanaka M, McConnell M, Iwakiri Y. Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats. Scientific Reports 2018, 8: 17983. PMID: 30573742, PMCID: PMC6301948, DOI: 10.1038/s41598-018-36297-0.
  • Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver.Cui J, Piotrowski-Daspit AS, Zhang J, Shao M, Bracaglia LG, Utsumi T, Seo YE, DiRito J, Song E, Wu C, Inada A, Tietjen GT, Pober JS, Iwakiri Y, Saltzman WM. Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver. Journal Of Controlled Release : Official Journal Of The Controlled Release Society 2019, 304: 259-267. PMID: 31054286, PMCID: PMC6613984, DOI: 10.1016/j.jconrel.2019.04.044.
  • Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation.Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2019, 317: G387-G397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.
  • O-GlcNAc transferase suppresses necroptosis and liver fibrosis.Zhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, Chung D, Robert ME, Ehrlich BE, Bennett AM, Yu J, Nathanson MH, Yang X. O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight 2019, 4 PMID: 31672932, PMCID: PMC6948774, DOI: 10.1172/jci.insight.127709.
  • Endothelial Leukocyte Cell-Derived Chemotaxin 2/Tyrosine Kinase With Immunoglobulin-Like and Epidermal Growth Factor-Like Domains 1 Signaling in Liver Fibrosis.Su T, Iwakiri Y. Endothelial Leukocyte Cell-Derived Chemotaxin 2/Tyrosine Kinase With Immunoglobulin-Like and Epidermal Growth Factor-Like Domains 1 Signaling in Liver Fibrosis. Hepatology (Baltimore, Md.) 2020, 72: 347-349. PMID: 32060947, DOI: 10.1002/hep.31183.
  • Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity.Zhang S, Guo F, Yu M, Yang X, Yao Z, Li Q, Wei Z, Feng K, Zeng P, Zhao D, Li X, Zhu Y, Miao QR, Iwakiri Y, Chen Y, Han J, Duan Y. Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity. Journal Of Hepatology 2020, 73: 1482-1495. PMID: 32738448, DOI: 10.1016/j.jhep.2020.07.034.
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