ROCK2 regulates TGF- β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells.

ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in the mesangial cells. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Nagai Y, Matoba K, Kawanami D, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K, Nishimura R Abstract The small GTPase Rho and its effector Rho-kinase are involved in the pathogenesis of diabetic kidney disease. Rho-kinase has two isoforms, ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic mediators. Glomeruli isolated from type 2 diabetic db/db mice demonstrated increased gene expression of transforming growth factor β (TGF-β) and its downstream profibrotic mediators. Chemical inhibition of Rho-kinase suppressed the expression of profibrotic mediators in both isolated glomeruli and cultured mesangial cells. An investigation of mechanisms underlying this observation revealed activated Rho-kinase functions through the phosphorylation of JNK and Erk, and the nuclear translocation of nuclear factor-kappa B via actin dynamics. Knockdown by small interfering RNA against ROCK1 and ROCK2 showed that ROCK2 but not ROCK1 controls this fibrotic machinery. A further in vivo study showed that ROCK2 activity in the renal cortex of db/db mice was elevated compared to control db/m mice. Importantly, oral administration of ROCK2 inhibitor attenua...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research