RGD Reference Report - Activin A stimulates the proliferation and differentiation of cardiac fibroblasts via the ERK1/2 and p38-MAPK pathways. - Rat Genome Database

RGD Reference Report - Activin A stimulates the proliferation and differentiation of cardiac fibroblasts via the ERK1/2 and p38-MAPK pathways. - Rat Genome Database

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Activin A stimulates the proliferation and differentiation of cardiac fibroblasts via the ERK1/2 and p38-MAPK pathways.
Authors:	Hu, Juan Wang, Xi Wei, Shao-Ming Tang, Yan-Hong Zhou, Qin Huang, Cong-Xin
Citation:	Hu J, etal., Eur J Pharmacol. 2016 Oct 15;789:319-327. doi: 10.1016/j.ejphar.2016.07.053. Epub 2016 Jul 29.
RGD ID:	151665478
Pubmed:	PMID:27477354 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.ejphar.2016.07.053 (Journal Full-text)
Activin A is a key regulator of cardiac fibrosis. However, little is known about the mechanisms by which it contributes to cardiac fibrosis. Our study explored the effects of activin A on proliferation and differentiation of adult rat cardiac fibroblasts (CFs) via the activin A receptor, activin receptor-like kinase 4 (ALK4). CF proliferation was measured by CCK8 and EdU assays, while differentiation, fibrosis and signaling were measured by western blot analysis of α-smooth muscle actin, collagen type I, phosphorylated extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (p38-MAPK) expression. Activin A levels were measured by ELISA and western blot analysis. We demonstrated that CFs express activin A and its expression was significantly enhanced by angiotensin II (Ang II), but follistatin (activin A inhibitor) significantly reversed Ang II-induced activin A upregulation, CF proliferation, differentiation, collagen type I expression as well as ERK1/2 and p38-MAPK pathways activation. Conversely, recombinant activin A largely increased these parameters in both the presence and absence of Ang II. Interestingly, p38-MAPK (SB203580) and ALK4 (SB431542) inhibitors significantly reduced all activin A-mediated responses; however, an ERK1/2 inhibitor (PD98059) could only significantly reduce CF proliferation and collagen type I expression but not differentiation. Importantly, the most significant effects were observed in the presence vs. absence of Ang II. Thus, activin A promotes basal and Ang II-induced CF proliferation and differentiation via ALK4, and the effects are partly mediated through the ERK1/2 and p38-MAPK pathways. These data suggest that activin A is a potential therapeutic target for cardiac fibrosis.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Acvr1b	Rat	cardiac fibroblast cell development		IMP			RGD
Inhba	Rat	cardiac fibroblast cell development		IDA			RGD
Inhba	Rat	cellular response to angiotensin		IEP			RGD
Acvr1b	Rat	positive regulation of collagen biosynthetic process		IMP			RGD
Inhba	Rat	positive regulation of collagen biosynthetic process		IDA			RGD
Inhba	Rat	positive regulation of ERK1 and ERK2 cascade		IDA			RGD

Objects Annotated

Genes (Rattus norvegicus)

Acvr1b (activin A receptor type 1B)

Inhba (inhibin subunit beta A)

Additional Information