Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease

Journal of the American Society of Nephrology : JASN
Yiqing GuoSandeep K Mallipattu

Abstract

Podocyte injury is the hallmark of proteinuric kidney diseases, such as FSGS and minimal change disease, and destabilization of the podocyte's actin cytoskeleton contributes to podocyte dysfunction in many of these conditions. Although agents, such as glucocorticoids and cyclosporin, stabilize the actin cytoskeleton, systemic toxicity hinders chronic use. We previously showed that loss of the kidney-enriched zinc finger transcription factor Krüppel-like factor 15 (KLF15) increases susceptibility to proteinuric kidney disease and attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte. We induced podocyte-specific KLF15 in two proteinuric murine models, HIV-1 transgenic (Tg26) mice and adriamycin (ADR)-induced nephropathy, and used RNA sequencing of isolated glomeruli and subsequent enrichment analysis to investigate pathways mediated by podocyte-specific KLF15 in Tg26 mice. We also explored in cultured human podocytes the potential mediating role of Wilms Tumor 1 (WT1), a transcription factor critical for podocyte differentiation. In Tg26 mice, inducing podocyte-specific KLF15 attenuated podocyte injury, glomerulosclerosis, tubulointerstitial fibrosis, and inflammation, while improving renal functio...Continue Reading

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Citations

Jun 1, 2019·Expert Opinion on Therapeutic Targets·Paola CassisGiuseppe Remuzzi
May 30, 2019·The Biochemical Journal·Yanyan GuoXiaoqiang Guo
Sep 19, 2020·Nature Reviews. Nephrology·Shipra AgrawalPierre-Louis Tharaux
Nov 15, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Heidy Hendra, Alan D Salama
Mar 2, 2021·American Journal of Physiology. Renal Physiology·Anqun ChenJohn Cijiang He

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