Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney.
- Author:
Eun Hui BAE
1
;
In Jin KIM
;
Yoon Wha OH
;
Woo Kyun BAE
;
Jeong Woo PARK
;
Seong Kwon MA
;
Nam Ho KIM
;
Ki Chul CHOI
;
Jong Un LEE
;
Suhn Hee KIM
;
Soo Wan KIM
Author Information
1. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. skimw@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Gentamicin;
Endothelin;
Aldosterone synthase;
Transforming growth factor-beta1
- MeSH:
Aldosterone Synthase*;
Animals;
Creatinine;
Endothelin-1*;
Endothelins;
Gentamicins;
Humans;
Immunoblotting;
Immunohistochemistry;
Kidney*;
Male;
Peptidyl-Dipeptidase A;
Rats*;
Rats, Sprague-Dawley;
Real-Time Polymerase Chain Reaction;
Receptors, Mineralocorticoid;
Renal Insufficiency;
Renin;
Renin-Angiotensin System;
RNA, Messenger;
Transforming Growth Factor beta;
Transforming Growth Factor beta1
- From:Korean Journal of Nephrology
2007;26(6):660-668
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats. METHODS: Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry. RESULTS: Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed. CONCLUSION: The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.
