Transforming growth factor-beta1 induces collagen synthesis and accumulation via p38 mitogen-activated protein kinase (MAPK) pathway in cultured L(6)E(9) myoblasts.

Transforming growth factor-beta (TGF-beta) plays a pivotal role in the extracellular matrix accumulation observed in chronic progressive tissue fibrosis, but the intracellular signaling mechanism by which TGF-beta stimulates this process remains poorly understood. We examined whether mitogen-activated protein kinase (MAPK) routes were involved in TGF-beta1-induced collagen expression in L(6)E(9) myoblasts. TGF-beta1 induced p38 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation whereas no effect on Jun N-terminal kinase phosphorylation was observed. Biochemical blockade of p38 but not of the ERK MAPK pathway abolished TGF-beta1-induced alpha(2)(I) collagen mRNA expression and accumulation. These data indicate that TGF-beta1-induced p38 activation is involved in TGF-beta1-stimulated collagen synthesis.

Endoglin expression in human and rat mesangial cells and its upregulation by TGF-beta1.

Endoglin is a component of the TGF-beta receptor complex present in the kidney at the human glomerular mesangium. Since the cellular origin of the glomerular endoglin is unknown, in the present study we investigated the expression of endoglin in mesangial cells in culture, as well as their response to TGF-beta1. Western and Northern blot analysis identified the expression of endoglin protein and mRNA transcript in both human and rat mesangial cells. Flow cytometry and immunocytochemistry analyses revealed that endoglin is present on the cell membrane. Exogenous TGF-beta1 stimulated not only the expression of collagen alpha1 (I) I and TGF-beta1, but also that of endoglin. These data provide the first evidence for the expression of endoglin in mesangial cells, as well as its upregulation by TGF-beta1, thus suggesting that endoglin may have a role in modulating the effects of TGF-beta1 on the glomerular mesangium.