Regulation of Renin Expression by Β1-Integrin in As4.1 Juxtaglomerular Line Cells
Nobumichi Saito,
Masao Toyoda,
Masumi Kondo,
Makiko Abe,
Noriyuki Sanechika,
Moritsugu Kimura,
Kaichiro Sawada,
Masafumi Fukagawa
Affiliations
Nobumichi Saito
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Masao Toyoda
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Masumi Kondo
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Makiko Abe
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Noriyuki Sanechika
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Moritsugu Kimura
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Kaichiro Sawada
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
Masafumi Fukagawa
Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan
(1) Background: Renal dysfunction and hypertension are mutually aggravating factors; however, the details of their interaction remain unclear. In a study using renal tissue from diabetic rats, we found that β1-integrin, a cell-substrate adhesion molecule, is specifically phosphorylated in juxtaglomerular cells that secrete renin, a blood pressure regulator. (2) Methods: A mouse juxtaglomerular cell line (As4.1 cells) was used for the following experiments: drug-induced promotion of β1-integrin phosphorylation/dephosphorylation; knockdown of β1-integrin and the cell adhesion molecule connexin-40 (a candidate for the main body of baroreceptor); and pressurization to atmospheric pressure + 100 mmHg. culture in hypotonic liquid medium. The expression of renin under these conditions was measured by qRT-PCR. (3) Results: Phosphorylation of β1-integrin suppressed the expression of renin, while dephosphorylation conversely promoted it. β1-integrin and connexin-40 knockdown both promoted the expression of renin. Pneumatic pressurization and hypotonic medium culture both decreased the expression of renin, which was restored by the knockdown of β1-integrin. (4) Conclusions: β1-integrin plays an inhibitory role in the regulation of the expression of renin, which may be controlled by phosphorylation and dephosphorylation. It is hypothesized that β1-integrin and other adhesion factors regulate the expression of renin by altering the sensitivity of baroreceptors on the plasma membrane.
