ROCK2-induced Metabolic Rewiring in Diabetic Podocytopathy

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Apr 9

PMID 35396346

Authors

Keiichiro Matoba

Yusuke Takeda

Yosuke Nagai

Kensuke Sekiguchi

Rikako Ukichi

Hiroshi Takahashi

Daisuke Aizawa

Masahiro Ikegami

Toshiaki Tachibana

Daiji Kawanami

Yasushi Kanazawa

Tamotsu Yokota

Kazunori Utsunomiya

Rimei Nishimura

Affiliations

Soon will be listed here.

Abstract

Loss of podocytes is a common feature of diabetic renal injury and a key contributor to the development of albuminuria. We found that podocyte Rho associated coiled-coil containing protein kinase 2 (ROCK2) is activated in rodent models and patients with diabetes. Mice that lacked ROCK2 only in podocytes (PR2KO) were resistant to albuminuria, glomerular fibrosis, and podocyte loss in multiple animal models of diabetes (i.e., streptozotocin injection, db/db, and high-fat diet feeding). RNA-sequencing of ROCK2-null podocytes provided initial evidence suggesting ROCK2 as a regulator of cellular metabolism. In particular, ROCK2 serves as a suppressor of peroxisome proliferator-activated receptors α (PPARα), which rewires cellular programs to negatively control the transcription of genes involved in fatty acid oxidation and consequently induce podocyte apoptosis. These data establish ROCK2 as a nodal regulator of podocyte energy homeostasis and suggest this signaling pathway as a promising target for the treatment of diabetic podocytopathy.

Citing Articles

Conditional deficiency of Rho-associated kinases disrupts endothelial cell junctions and impairs respiratory function in adult mice.

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