Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices

Lingling Jiang; Yan Qi; Xianghan Kong; Runnan Wang; Jianfei Qi; Francis Lin; Xueling Cui; Zhonghui Liu

doi:10.3389/fcell.2021.660316

Activin A as a Novel Chemokine Induces Migration of L929 Fibroblasts by ERK Signaling in Microfluidic Devices

Front Cell Dev Biol. 2021 May 21:9:660316. doi: 10.3389/fcell.2021.660316. eCollection 2021.

Authors

Lingling Jiang^{1

2}, Yan Qi², Xianghan Kong², Runnan Wang³, Jianfei Qi⁴, Francis Lin⁵, Xueling Cui³, Zhonghui Liu²

Affiliations

¹ Department of Oral Comprehensive Therapy, School and Hospital of Stomatology, Jilin University, Changchun, China.
² Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China.
³ Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China.
⁴ Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, United States.
⁵ Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, Canada.

Abstract

Activin A, a member of the transforming growth factor-beta (TGF-β) superfamily, contributes to tissue healing and fibrosis. As the innate tissue cells, fibroblasts also play an important role in wound healing and fibrosis. Herein, this study was aimed to investigate how activin A exhibited regulatory effects on adhesion and migration of fibroblasts. We found that activin A induced the migration of fibroblast cell line L929 cells in transwell chamber and microfluidic device. Activin A also promoted L929 cells adhesion, but did not affect L929 cells viability or proliferation. In addition, activin A induced α-SMA expression and TGF-β1 release, which were factors closely related to tissue fibrosis, but had no effect on IL-6 production, a pro-inflammatory cytokine. Furthermore, activin A elevated calcium levels in L929 cells and increased p-ERK protein levels. Activin A-induced migration of L929 cells was attenuated by ERK inhibitor FR180204. To conclude, these data indicated that activin A as a novel chemokine induced the chemotactic migration of L929 cells via ERK signaling and possessed the pro-fibrosis role. These findings provide a new insight into understanding of activin A in tissue fibrosis.

Keywords: ERK; activin A; fibroblasts; microfluidic device; migration.