SMAD-Independent Down-Regulation of Caveolin-1 by TGF-β: Effects on Proliferation and Survival of Myofibroblasts

• DOI: 10.1371/journal.pone.0116995
• Publication Date: 2015-02-06T21:34:44Z
• Authors: Yan Y. Sanders; Zongbin Cui; Claude Jourdan Le...; Jeffrey C. Horowitz; Sunad Rangarajan; Ashish Kurundkar; Veena B. Antony; Victor J. Thannickal
• Keywords: Myofibroblast; Caveolin 1

Transforming growth factor-β (TGF-β) mediates growth-inhibitory effects on most target cells via activation of the canonical SMAD signaling pathway. This activity may be coupled with cellular differentiation. Our studies demonstrate that TGF-β1 inhibits proliferation primary, non-transformed human lung fibroblasts in association induction myofibroblast Differentiated myofibroblasts maintain capacity to proliferate response exogenous mitogenic stimuli and are resistant serum deprivation-induced apoptosis. These proliferative anti-apoptotic properties related, part, down-regulation caveolin-1 (Cav-1) by TGF-β1. Cav-1 is mediated early p38 MAPK does not require signaling. In contrast, differentiation dependent pathway, but MAPK. Thus, combinatorial pathways, respectively, confer apoptosis-resistant myofibroblasts. Selective targeting this SMAD-independent, p38-MAPK/Cav-1-dependent pathway likely effective treatment pathological conditions characterized TGF-β activation.