A serine protease inhibitor camostat mesilate prevents podocyte apoptosis and attenuates podocyte injury in metabolic syndrome model rats.

Abstract

Metabolic syndrome (MetS) is associated with chronic kidney disease and proteinuria. Previously, we reported that a synthetic serine protease inhibitor, camostat mesilate (CM), mitigated hypertension and proteinuria in rodent disease models. The present study evaluated the anti-hypertensive and anti-proteinuric effects of CM in MetS model rats (SHR/ND mcr-cp). Rats were divided into normal salt-fed (NS), high salt-fed (HS), HS and CM-treated (CM), and HS and hydralazine-treated (Hyd) groups. Rats were sacrificed after four weeks of treatment. Severe hypertension and proteinuria were observed in the HS group. Although CM and Hyd equally alleviated hypertension, CM suppressed proteinuria and glomerular sclerosis more efficiently than Hyd. The HS group revealed a decrease in podocyte number and podocyte-specific molecules, together with an increase in glomerular apoptotic cells and apoptosis-related proteins in the kidney. These changes were significantly attenuated by CM, but not by Hyd. Furthermore, CM ameliorated the apoptotic signals in murine cultured podocytes stimulated with the high glucose and aldosterone medium. In conclusion, CM could exert renoprotective effects in MetS model rats, together with the inhibition of podocyte apoptosis. Our study suggests that serine protease inhibition may become a new therapeutic strategy against MetS-related hypertension and renal injuries.

• Authors: Teruhiko Mizumoto, Yutaka Kakizoe, Terumasa Nakagawa, Yasunobu Iwata, Yoshikazu Miyasato, Kohei Uchimura, Masataka Adachi, Qinyuan Deng, Manabu Hayata, Jun Morinaga, Taku Miyoshi, Yuichiro Izumi, Takashige Kuwabara, Yoshiki Sakai, Kimio Tomita, Kenichiro Kitamura, Masashi Mukoyama
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 146 Issue 4 Pg. 192-199 (Aug 2021) ISSN: 1347-8648 [Electronic] Japan
• PMID: 34116732 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Esters
• Guanidines
• Protease Inhibitors
• camostat

Topics

• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Esters (pharmacology)
• Guanidines (pharmacology)
• Hypertension (drug therapy, etiology)
• Male
• Metabolic Syndrome (complications, pathology)
• Mice
• Podocytes (pathology)
• Protease Inhibitors (pharmacology)
• Proteinuria (drug therapy, etiology)
• Rats, Inbred SHR
• Renal Insufficiency, Chronic (drug therapy, etiology)