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http://dx.doi.org/10.4196/kjpp.2022.26.6.479

Cell-cell contacts via N-cadherin induce a regulatory renin secretory phenotype in As4.1 cells  

Chang, Jai Won (Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine)
Kim, Soohyun (Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine)
Lee, Eun Young (Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital)
Leem, Chae Hun (Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine)
Kim, Suhn Hee (Department of Physiology, Jeonbuk National University Medical School)
Park, Chun Sik (Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.26, no.6, 2022 , pp. 479-499 More about this Journal
Abstract
The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.
Keywords
MRTF-A; Myosin light chain; Myosin light-chain kinase; Myosin light chain phosohatase-1; N-cadherin; Phenotype switching;
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