Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney

Korean Journal of Nephrology 2007;26(6):660-668.

Eun Hui Bae, M.D.1, In Jin Kim, M.S.2 , Yoon Wha Oh, Ph.D.2 Woo Kyun Bae, M.D.1 , Jeong Woo Park, M.D.1, Seong Kwon Ma, M.D.1 Nam Ho Kim, M.D.1, Ki Chul Choi, M.D.1 , Jong Un Lee, M.D.2 Suhn Hee Kim, M.D.3 and Soo Wan Kim, M.D.1

Departments of Internal Medicine1 and Physiology²
Chonnam National University Medical School, Gwangju, Korea Department of Physiology³
Chonbuk National University Medical School, Jeonju, Korea

원저 : Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney

Departments of Internal Medicine1 and Physiology2, Chonnam National University Medical School, Gwangju, Korea Department of Physiology3, Chonbuk National University Medical School, Jeonju, Korea

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-β1 (TGF-β1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-β 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-β1 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.

Key Words: Gentamicin, Endothelin, Aldosterone synthase, Transforming growth factor-β1