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

• 영문명: Cell-cell contacts via N-cadherin induce a regulatory renin secretory phenotype in As4.1 cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Jai Won Chang Soohyun Kim Eun Young Lee Chae Hun Leem Suhn Hee Kim Chun Sik Park
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제26권 제6호, 479~499쪽, 전체 21쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2022.11.30

영문 초록

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.

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키워드

MRTF-A Myosin light chain Myosin light-chain kinase Myosin light chain phosohatase-1 N-cadherin Phenotype switching