High glucose-induced fibronectin upregulation in cultured mesangial cells involves caveolin-1-dependent RhoA-GTP activation via Src kinase.
Mol Med Rep
; 14(1): 963-8, 2016 Jul.
Article
en En
| MEDLINE
| ID: mdl-27220778
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 HGinduced FN upregulation. HGinduced RhoA activation was prevented by inhibiting caveolae with filipin III or caveolin1 siRNA and rescued by exogenous caveolin1. 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 caveolin1 on Y14 has also been implicated in signaling responses. Overexpression of the nonphosphorylatable caveolin1 Y14A mutant prevented the HGinduced RhoA activation and FN upregulation. In conclusion, HGinduced FN upregulation requires caveolae and caveolin1 to interact with RhoA and Src kinases. Interference with Src/caveolin-1/RhoA signaling may provide novel mechanistic targets for the treatment of DKD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibronectinas
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Familia-src Quinasas
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Proteína de Unión al GTP rhoA
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Células Mesangiales
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Caveolina 1
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Glucosa
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2016
Tipo del documento:
Article