A serine protease inhibitor camostat mesilate prevents podocyte apoptosis and attenuates podocyte injury in metabolic syndrome model rats
Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:146 |
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| Enthalten in: |
Journal of pharmacological sciences - 146(2021), 4 vom: 20. Aug., Seite 192-199 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mizumoto, Teruhiko [VerfasserIn] |
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| Links: |
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| Themen: |
0FD207WKDU |
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| Anmerkungen: |
Date Completed 12.11.2021 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jphs.2021.04.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326646787 |
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| 100 | 1 | |a Mizumoto, Teruhiko |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A serine protease inhibitor camostat mesilate prevents podocyte apoptosis and attenuates podocyte injury in metabolic syndrome model rats |
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| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Camostat mesilate | |
| 650 | 4 | |a Metabolic syndrome | |
| 650 | 4 | |a Podocyte injury | |
| 650 | 4 | |a Proteinuria | |
| 650 | 4 | |a Serine protease | |
| 650 | 7 | |a Esters |2 NLM | |
| 650 | 7 | |a Guanidines |2 NLM | |
| 650 | 7 | |a Protease Inhibitors |2 NLM | |
| 650 | 7 | |a camostat |2 NLM | |
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| 700 | 1 | |a Kakizoe, Yutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Nakagawa, Terumasa |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Yasunobu |e verfasserin |4 aut | |
| 700 | 1 | |a Miyasato, Yoshikazu |e verfasserin |4 aut | |
| 700 | 1 | |a Uchimura, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Adachi, Masataka |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Qinyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hayata, Manabu |e verfasserin |4 aut | |
| 700 | 1 | |a Morinaga, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Miyoshi, Taku |e verfasserin |4 aut | |
| 700 | 1 | |a Izumi, Yuichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kuwabara, Takashige |e verfasserin |4 aut | |
| 700 | 1 | |a Sakai, Yoshiki |e verfasserin |4 aut | |
| 700 | 1 | |a Tomita, Kimio |e verfasserin |4 aut | |
| 700 | 1 | |a Kitamura, Kenichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Mukoyama, Masashi |e verfasserin |4 aut | |
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