Semaphorin7A (SEMA7A) is a membrane-anchored protein involved in immune and inflammatory responses, exerting an effect on pulmonary fibrosis. Thus, we aimed to investigate the role of SEMA7A in hepatic fibrosis. Liver injury was induced in vivo by carbon tetrachloride i.p. injection or bile duct ligation in wild-type and SEMA7A knockout (KO) mice. Human and mouse liver samples and primary mouse hepatic cell populations were used for Western blot analysis, quantitative real-time RT-PCR, and immunohistochemistry. SEMA7A is highly expressed in hepatic stellate cells (HSCs). The expression of SEMA7A and its receptor β1-integrin subunit increase during liver injury and in activated HSCs. Transforming growth factor β-stimulated HSCs showed increased expression of SEMA7A in a SMAD2/3-independent manner, leading to increased expression of fibrogenic and inflammation markers. This pattern was significantly blunted in SEMA7A KO HSCs. Overexpression of SEMA7A in HSCs showed increased fibrogenic and inflammation markers expression. In vivo, SEMA7A KO mice treated with carbon tetrachloride and bile duct ligation developed reduced fibrosis versus wild-type mice. Moreover, SEMA7A expression increased in liver samples of patients with fibrosis versus healthy controls. SEMA7A was expressed in the liver and was increased in the course of liver fibrosis, both in mice and in humans. SEMA7A was mainly expressed in HSCs with respect to other cell types in the liver and plays a critical role in regulating fibrosis.
Semaphorin 7A contributes to TGF-β-mediated liver fibrogenesis / De Minicis, S; Rychlicki, C; Agostinelli, L; Saccomanno, S; Trozzi, L; Candelaresi, C; Bataller, R; Millán, C; Brenner, Da; Vivarelli, Marco; Mocchegiani, Federico; Marzioni, Marco; Benedetti, Antonio; Svegliati Baroni, G.. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - STAMPA. - 183:3(2013), pp. 820-830. [10.1016/j.ajpath.2013.05.030]