A new study by Leslie Gewin, MD, Associate Professor of Medicine, WashU Nephrology, challenges the long-held assumption that renal tubular cell cycle progression is always beneficial in the context of renal injury.
In their article, just published online in Journal of Clinical Investigation (JCI) Insight, Dr. Gewin and colleagues detail how slowing cell cycle progression at G1/S using palbociclib, an FDA-approved CDK4/6 inhibitor, protected against tubule injury, renal functional decline, and tubulointerstitial fibrosis in two models of chronic kidney disease. Treatment of kidney tubule cells with palbociclib protected against cell death through a STAT3/IL-1b pathway. In humans, reduced expression of the CDK inhibitor CDKN2B was linked to impaired kidney function, consistent with the murine studies.
The article, Blocking Cell Cycle Progression Through CDK4/6 Protects Against Chronic Kidney Disease, will be featured in the JCI This Month print digest for the July 2022 issue. Authors: Yosuke Osaki, Marika Manolopoulou, Alla V. Ivanova, Nicholas Vartanian, Melanie Phillips Mignemi, Justin Kern, Jianchun Chen, Haichun Yang, Agnes B. Fogo, Mingzhi Zhang, Cassianne Robinson-Cohen, Leslie S. Gewin.
“Tubule cell cycle progression is important after an acute injury to facilitate repair,” says Dr. Gewin. “Others have shown that ongoing tubule cell cycle progression is present in kidney biopsies from patients with chronic kidney disease, but it was unclear whether this is adaptive or maladaptive. Our data suggest that, in contrast to acute kidney injury, ongoing tubular cell cycle progression in chronic kidney disease may be maladaptive.”
Read more about Dr. Gewin here and visit theGewin Lab. On Twitter, follow @LeslieGewin and keep up to date with our Division @WUNephrology.