Up-regulation of TGF-β via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells

  • Authors:
    • Wei Song
    • Ying Zhang
    • Chen Jia
    • Lili Ren
    • Yumei Mi
    • Yan Lu
    • Yinong Jiang
  • View Affiliations

  • Published online on: October 3, 2011     https://doi.org/10.3892/mmr.2011.615
  • Pages: 223-227
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Abstract

Prorenin is thought to be an inactive precursor of renin. This study investigated whether human prorenin was capable of activating the (pro)renin receptors [(P)RRs], leading to the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal mesangial cells (HRMCs). HRMCs cultured in vitro were pretreated with an AT1 and AT2 blocker prior to stimulation by prorenin, PD98059 (an inhibitor of ERK1/2) and handle-region peptide (HRP). Phosphorylated ERK1/2 was evaluated using Western blot analysis, and the concentration of TGF-β was measured by ELISA. The mRNA of TGF-β was evaluated by RT-PCR. It was found that prorenin activated the (P)RR in cultured HRMCs, which in turn increased p-ERK1/2. Prorenin induced rapid phosphorylation of ERK1/2 and increased p-ERK1/2 in a time- and dose-dependent manner. The protein levels of TGF-β increased significantly with the stimulation of prorenin. PD98059 significantly decreased p-ERK1/2 and then downregulated TGF-β. HRP did not inhibit either ERK1/2 phosphorylation or the increase in TGF-β. ERK1/2 phosphorylation induced by prorenin led to a marked increase in TGF-β. The regulation of TGF-β was highly dependent on ERK1/2. Thus, ERK1/2 may play a key role in the development of kidney disease. HRP neither affects the ERK1/2 signaling nor the level of TGF-β in HRMCs.

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January 2012
Volume 5 Issue 1

Print ISSN: 1791-2997
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Spandidos Publications style
Song W, Zhang Y, Jia C, Ren L, Mi Y, Lu Y and Jiang Y: Up-regulation of TGF-β via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells. Mol Med Rep 5: 223-227, 2012.
APA
Song, W., Zhang, Y., Jia, C., Ren, L., Mi, Y., Lu, Y., & Jiang, Y. (2012). Up-regulation of TGF-β via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells. Molecular Medicine Reports, 5, 223-227. https://doi.org/10.3892/mmr.2011.615
MLA
Song, W., Zhang, Y., Jia, C., Ren, L., Mi, Y., Lu, Y., Jiang, Y."Up-regulation of TGF-β via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells". Molecular Medicine Reports 5.1 (2012): 223-227.
Chicago
Song, W., Zhang, Y., Jia, C., Ren, L., Mi, Y., Lu, Y., Jiang, Y."Up-regulation of TGF-β via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells". Molecular Medicine Reports 5, no. 1 (2012): 223-227. https://doi.org/10.3892/mmr.2011.615