October 5, 2020

Clue to diabetic kidney disease

Vanderbilt researchers have identified a signaling pathway that promotes kidney fibrosis in patients with diabetes — and that could be targeted with an existing approved medication.

Diabetic patients can develop kidney disease since high levels of glucose damage blood vessels, prompting accumulation of scarred tissue with reduced kidney function. Recent studies have suggested that progressive interstitial fibrosis in the renal proximal tubule is an important mediator in the development of diabetic nephropathy. 

Reporting in the journal Diabetes, Jianchun Chen, MD, Raymond Harris, MD, and colleagues observed increased expression and activation of YAP (Yes-associated protein) in renal proximal tubule epithelial cells in diabetic patient and mouse kidneys.  

Fibrosis was significantly reduced when the gene encoding YAP was deleted in these cells or the YAP protein was blocked with verteporfin, a drug approved for the treatment of macular degeneration. 

The researchers also identified upstream YAP-dependent mechanisms that lead to release of a growth factor activating the deposition of the building blocks needed for scar tissue formation. Targeting this signaling pathway and repurposing verteporfin thus may be a therapeutic strategy to reduce renal fibrosis in patients with diabetes.

This research was supported by grants from the American Diabetes Association, National Institutes of Health (DK051265, DK062794 and DK079341) and the U.S. Department of Veterans Affairs.