The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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)
  • Received : 2022.06.13
  • Accepted : 2022.09.19
  • Published : 2022.11.01
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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

Acknowledgement

This article is dedicated to my mentor, distinguished professor Suk Ki Hong (October 16, 1928-October 4, 1999) at the University at Buffalo. His unrelenting enthusiasm, optimism, and encouragement have been instrumental in shaping the course my scientific career as a physiologist (CS Park) and many other young scientists at Yonsei University, Seoul Korea and the State University of New York at Buffalo, USA. We would like to thank to Dr. Astrid C. Hauge-Evans at the University of Roehampton, UK, for information regarding differences in insulin secretion between MIN6 monolayers and pseudoislets and Dr. Kathleen A. Martin at Yale University, USA, for her very insightful discussion. We are also indebted to Mrs. Julie Edwards at Boehringer Ingelheim for providing the compound BILA 2157 BS.

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