Elevated hydrostatic pressure enhances migration of fibroblast through autocrined TGF-β₁ and filamin A upregulation

Yu-Chiu Kao^1,2*, Zih-Hua Chen¹, Wen-Yu Wang¹, Po-Ling Kuo^1,3,4, Chau-Hwang Lee^2,5

¹Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
²Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan
³Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
⁴Department of Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
⁵Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan

* Presenter:Yu-Chiu Kao, email:winipinky@gmail.com

Fibroblast migration plays a pivotal role in many pathophysiological conditions, such as wound healing, cancer invasion, and tissue inflammation. Elevated interstitial hydrostatic pressure (HP) is a hallmark in many pathological and physiological conditions, such as solid tumors and tissue edema resulting from damage or inflammation [1]. We had verified that 20 mmHg HP could increase the motility of lung cancer cells through the upregulation of aquaporin and the phosphorylation of ERK1/2 [2]. However, it was not clear if HP could also influence the migration of other types of cells. In the present work, we applied HP of 20 cmH2O (14.7 mmHg) to cultured fibroblasts to simulate the elevated interstitial-HP conditions. We found that the migration speed of fibroblasts was increased by 33%, accompanied with a ~19% increase of autocrined transforming growth factor-β1 (TGF-β1). The HP-induced migration increase was suppressed by the TGF-β1 receptor inhibitor. Protein analyses revealed that the HP-induced migration acceleration correlated with the upregulation of filamin A, one of the principal proteins responsible for migration initiation [3]. Filamin A knockdown by siRNA significantly abolished the HP-induced migration acceleration. Our findings highlight the importance of elevated interstitial HP in the migration of fibroblasts.

Keywords: Fibroblast, Interstitial hydrostatic pressure, Filamin, TGF-β