Extracellular matrix-induced Hic-5 expression in glomerular mesangial cells leads to a prosclerotic phenotype independent of TGF-{beta} [Research Communication]

Chronic fibroproliferative diseases account for approximately 45% of all deaths in the developed world. In the kidney, glomerulosclerosis is the underlying pathology in approximately half of patients with renal failure receiving dialysis. Mesangial cell expression of the LIM protein hydrogen peroxide-induced clone-5 (Hic-5) is important in its pathogenesis. Hic-5 expression increases following mesangial cell attachment to collagen I, associated with increased collagen I expression and increased susceptibility to apoptosis both in vitro and in experimental glomerulosclerosis. TGF-β has an established role in many fibrotic diseases, including glomerulosclerosis, where it increases collagen I deposition in vivo and promotes mesangial cell apoptosis in vitro. In other cell types, TGF-β induces Hic-5 expression. We investigated whether Hic-5-induced changes in mesangial cell phenotype were TGF-β-dependent. Adding exogenous TGF-β to mesangial cell cultures failed to increase Hic-5 expression; blocking TGF-β signaling did not reduce Hic-5 expression. However, inducing Hic-5 expression in mesangial cells by adhesion to collagen I led to TGF-β expression, which was abolished by small interfering RNA (siRNA) Hic-5 knockdown. Mesangial cells expressing Hic-5 showed altered latent TGF-β-binding protein expression and Smad signaling, with enhanced susceptibility to TGF-β-induced apoptosis. Mesangial cell attachment to collagen I led to increased Hic...
Source: FASEB Journal - Category: Biology Authors: Tags: Research Communication Source Type: research