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MFS2 Regulation Controls Phosphate Excretion, Renal Stone Formation, Study Finds

June 25, 2019
by Julie Parry

A high phosphate diet caused stones within the Malpighian renal tubules and resulted in reduced lifespan of fruit flies, says new study led by Yale School of Medicine’s Clemens Bergwitz, MD, associate professor of medicine (endocrinology).

“In designing these experiments, we built on our earlier finding that MFS2 ablation caused hyperphosphatemia in flies and hypothesized that it was a key transporter for phosphate and that fibroblast growth factors (FGF) would regulate phosphate in fly blood,” said Bergwitz. “Our work suggests that fly FGF regulates phosphate transport in fly kidneys, just as FGF23 does in human kidneys.”

Bergwitz and his research team of Yale undergraduates designed experiments to understand the connection between phosphate, MFS2, the formation of renal stones within the Malpighian tubules (the kidneys of flies), and their link to lifespan of fruit flies. The team found that the fruit flies experienced a lifespan reduction when placed on high phosphate diet, which caused hyperphosphatemia and increased renal stones. They concluded that death was due to the renal stones themselves, rather than hyperphosphatemia.

“These findings have translational relevance to humans and the mortality observed in chronic kidney disease. The subtle, but important differences we observed in flies may point us to novel evolutionary conserved mechanisms that are relevant in humans,” explained Bergwitz.

Other authors are Yale’s Emily Rose, BS; Daniela Lee, BS; Emily Xiao; and Wenzhen Zhao, BS; and Mark Wee, and Jonathan Cohen of Massachusetts General Hospital.

Read the full paper, “Endocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules,” in Scientific Reports.

Submitted by Julie Parry on June 25, 2019