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July-2016 Volume 14 Issue 1

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Article

High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase

  • Authors:
    • Yongfu Lu
    • Lihong Tang
    • Yiqiao Li
    • Qiang He
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Zhejiang University School of Medicine, the First Affiliated Hospital, Hangzhou, Zhejiang 310003, P.R. China, Department of Clinical Laboratory, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, P.R. China, Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
  • Pages: 963-968
    |
    Published online on: May 19, 2016
       https://doi.org/10.3892/mmr.2016.5312
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Abstract

Increasing evidence indicates that diabetes-mediated renal interstitial fibrosis through extracellular matrix (ECM) protein accumulation is an important event in the development of diabetic kidney disease (DKD), however, the underlying mechanism remains unclear. In the current study, it was observed that high levels of glucose (HG) time‑ and dose-dependently increased the production of the ECM protein, fibronectin (FN), in primary rat mesangial cells. Inhibition of the Rho pathway blocked HG‑induced FN upregulation. HG‑induced RhoA activation was prevented by inhibiting caveolae with filipin III or caveolin‑1 siRNA and rescued by exogenous caveolin‑1. HG also increased caveolin-1/Src association and activated Src kinase, whereas the inhibition of Src blocked RhoA activation and FN upregulation. Src-mediated phosphorylation of caveolin‑1 on Y14 has also been implicated in signaling responses. Overexpression of the nonphosphorylatable caveolin‑1 Y14A mutant prevented the HG‑induced RhoA activation and FN upregulation. In conclusion, HG‑induced FN upregulation requires caveolae and caveolin‑1 to interact with RhoA and Src kinases. Interference with Src/caveolin-1/RhoA signaling may provide novel mechanistic targets for the treatment of DKD.
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Copy and paste a formatted citation
Spandidos Publications style
Lu Y, Tang L, Li Y and He Q: High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase. Mol Med Rep 14: 963-968, 2016.
APA
Lu, Y., Tang, L., Li, Y., & He, Q. (2016). High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase. Molecular Medicine Reports, 14, 963-968. https://doi.org/10.3892/mmr.2016.5312
MLA
Lu, Y., Tang, L., Li, Y., He, Q."High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase". Molecular Medicine Reports 14.1 (2016): 963-968.
Chicago
Lu, Y., Tang, L., Li, Y., He, Q."High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase". Molecular Medicine Reports 14, no. 1 (2016): 963-968. https://doi.org/10.3892/mmr.2016.5312
Copy and paste a formatted citation
x
Spandidos Publications style
Lu Y, Tang L, Li Y and He Q: High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase. Mol Med Rep 14: 963-968, 2016.
APA
Lu, Y., Tang, L., Li, Y., & He, Q. (2016). High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase. Molecular Medicine Reports, 14, 963-968. https://doi.org/10.3892/mmr.2016.5312
MLA
Lu, Y., Tang, L., Li, Y., He, Q."High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase". Molecular Medicine Reports 14.1 (2016): 963-968.
Chicago
Lu, Y., Tang, L., Li, Y., He, Q."High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase". Molecular Medicine Reports 14, no. 1 (2016): 963-968. https://doi.org/10.3892/mmr.2016.5312
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