TY - JOUR AB - The glomerular visceral epithelial cells, also termed podocytes, are key in maintaining the normal renal filtration barrier. Although it has been demonstrated that stimulation of c‑Maf inducing protein (CMIP) expression is involved in podocyte damage, the molecular events during this process remain unclear. In the current study, CMIP‑induced proximal signaling was investigated by focusing on its effect on cofilin‑1 activity in puromycin aminonucleoside (PA)‑damaged podocytes. An obvious elevation of CMIP expression and phosphorylated (p) cofilin‑1 levels was detected in cultured podocytes treated with PA and in glomeruli isolated from PA‑induced nephropathy rats. Stable knockdown of CMIP prevented upregulation of p‑cofilin‑1 and reorganization of actin cytoskeleton in PA‑treated podocytes. The activity of the Src family kinase Fyn was reduced, whereas small GTPase Ras homolog gene family, member A (RhoA) activity was increased in PA‑treated podocytes. Stimulation of CMIP expression inhibited Fyn activation and decreased the expression level of p‑p190RhoGAP, a negative regulator of RhoA activity. The level of p‑LIM domain kinase 1 (LIMK1), a downstream effector of RhoA, increased significantly in PA‑treated podocytes. Notably, the applications of RhoA inhibitor or knockdown of LIMK prevented increase of the p‑cofilin‑1 level in PA‑treated podocytes. Thus, the current data provided evidence that the CMIP/Fyn/RhoA/cofilin‑1 signaling pathway may be associated with actin disorganization and podocyte foot process spreading following podocyte injury. AD - Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China Department of Nephrology, The First People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China AU - Yu,Lixia AU - Ye,Jianming AU - Liu,Qifeng AU - Feng,Jianhua AU - Gu,Xiaoxia AU - Sun,Qiang AU - Lu,Guoyuan DA - 2017/10/01 DO - 10.3892/mmr.2017.7156 EP - 4963 IS - 4 JO - Mol Med Rep KW - podocyte c‑Maf inducing protein Ras homolog gene family member cofilin‑1 actin remodeling puromycin aminonucleoside PY - 2017 SN - 1791-2997 1791-3004 SP - 4955 ST - c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization T2 - Molecular Medicine Reports TI - c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization UR - https://doi.org/10.3892/mmr.2017.7156 VL - 16 ER -