Insulin-like growth factor binding protein-4 exerts antifibrotic activity by reducing levels of connective tissue growth factor and the C-X-C chemokine receptor 4.

ABSTRACT: The Insulin-like growth factor (IGF) system plays an important role in variety cellular biological functions; we previously reported levels of IGF binding proteins (IGFBP) -3 and -5 are increased in dermal and pulmonary fibrosis associated with the prototypic fibrosing disease systemic sclerosis (SSc), induce extracellular matrix (ECM) production, and promote fibrosis. We sought to examine the effects of another member of the family, IGFBP-4, on ECM production and fibrosis using cell-based, ex vivo organ culture and in vivo mouse lung fibrosis models. IGFBP-4 mRNA levels were significantly decreased in pulmonary fibroblasts of patients with SSc. ECM components were significantly reduced by endogenous and exogenous IGFBP-4. IGFBP-4 also blocked TGFβ-induced ECM production, and

SUBMITTER: Su Y 

PROVIDER: S-EPMC6720120 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature