Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9,TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats
10.3969/j.issn.1672-7347.2010.10.004
- VernacularTitle:自发性高血压大鼠Klotho与MMP-9, TIMP-1和PAI-1基因的表达及福辛普利和缬沙坦对其的干预作用
- Author:
Xiaomiao CHENG
;
Qiaoling ZHOU
;
Shudian LIN
;
Rong WU
- Publication Type:Journal Article
- Keywords:
Klotho;
MMP-9;
TIMP-1;
spontaneously hypertensive rat;
angiotensin Ⅱ;
renal interstitial fibrosis
- From:
Journal of Central South University(Medical Sciences)
2010;35(10):1048-1056
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the role of fosinopril and valsartan intervention in Klotho, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor (PAI-1) gene expression in hypertensive renal interstitial fibrosis (RIF) in the kidney tissue of spontaneously hypertensive rats (SHR). MethodsWe randomly divided 20 male 22-week-old SHR into 4 groups (5 in each group):a hypertension group (SHR group), a fosinopril group ［Fos group, 10 mg/( kg·d) gavage］, a valsartan group ［Val group, 10 mg/( kg·d) gavage］， and a fosinopril plus valsartan group ［Fos + Val group, fosinopril 10 mg/( kg·d) + valsartan 50 mg/( kg·d) gavage］. Another five 22-week-old male Wistar Kyoto rats (WKY) were used as controls. Through monitoring the weight of the rats, tail artery pressure, 24-hour urine protein by fosinopril and/or valsartan intervention after the 8-week trial. RT-PCR and Western blot were used to detect the mRNA and protein expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidneys.Results RT-PCR showed that in the SHR group, Klotho mRNA and protein expression were significantly decreased(P＜0.01), while mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 were significantly higher compared with the WKY group(P＜0.01). With fosinopril and / or valsartan intervention, Klotho mRNA expression in the Fos group (P＜0.01), Fos + Val group (P＜0.01), Val group (P＜0.05), Klotho protein expression in the Fos group(P＜0.05), Fos + Val group (P＜0.05), Val group (P＜0.01), were significantly increased compared with those in the SHR group. The mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 in the Fos group, Val group, and Fos + Val group were significantly lower than those in the SHR group (P＜0.01). The expression of Klotho mRNA had negative correlation with the expression of MMP-9 mRNA (r= -0.864, P<0.01), TIMP-1 mRNA (r=-0.725, P<0.01) and PAI-1 mRNA (r=-0.785, P<0.01). The Klotho protein expression had negative correlation with the expression of MMP-9 protein (r=-0.614, P<0.05), TIMP-1 protein (r=-0.579, P<0.05), and PAI-1 protein (r=-0.552, P<0.05). Conclusion Anti-aging gene Klotho and the genes related with extracellular matrix degradation gene MMP-9, TIMP-1, PAI-1 are involved in hypertensive renal injury. The expression of Klotho and MMP-9, TIMP-1, and PAI-1 is closely correlated. Fosinopril and valsartan which increase the Klotho mRNA and protein expression can alter the expression of Klotho-MMPs/TIMPs, which may be the main mechanism to prevent interstitial fibrosis.
