c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization

  • Authors:
    • Lixia Yu
    • Jianming Ye
    • Qifeng Liu
    • Jianhua Feng
    • Xiaoxia Gu
    • Qiang Sun
    • Guoyuan Lu
  • View Affiliations

  • Published online on: August 3, 2017     https://doi.org/10.3892/mmr.2017.7156
  • Pages: 4955-4963
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Abstract

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.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yu L, Ye J, Liu Q, Feng J, Gu X, Sun Q and Lu G: c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization. Mol Med Rep 16: 4955-4963, 2017
APA
Yu, L., Ye, J., Liu, Q., Feng, J., Gu, X., Sun, Q., & Lu, G. (2017). c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization. Molecular Medicine Reports, 16, 4955-4963. https://doi.org/10.3892/mmr.2017.7156
MLA
Yu, L., Ye, J., Liu, Q., Feng, J., Gu, X., Sun, Q., Lu, G."c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization". Molecular Medicine Reports 16.4 (2017): 4955-4963.
Chicago
Yu, L., Ye, J., Liu, Q., Feng, J., Gu, X., Sun, Q., Lu, G."c‑Maf inducing protein inhibits cofilin‑1 activity and alters podocyte cytoskeleton organization". Molecular Medicine Reports 16, no. 4 (2017): 4955-4963. https://doi.org/10.3892/mmr.2017.7156