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Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Oct; 35(10):1048-56.ZN

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).

METHODS

We 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.

Authors+Show Affiliations

Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China. cxm6131@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21051829

Citation

Cheng, Xiaomiao, et al. "Fosinopril and Valsartan Intervention in Gene Expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the Kidney of Spontaneously Hypertensive Rats." Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences, vol. 35, no. 10, 2010, pp. 1048-56.
Cheng X, Zhou Q, Lin S, et al. Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35(10):1048-56.
Cheng, X., Zhou, Q., Lin, S., & Wu, R. (2010). Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats. Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences, 35(10), 1048-56. https://doi.org/10.3969/j.issn.1672-7347.2010.10.004
Cheng X, et al. Fosinopril and Valsartan Intervention in Gene Expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the Kidney of Spontaneously Hypertensive Rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010;35(10):1048-56. PubMed PMID: 21051829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats. AU - Cheng,Xiaomiao, AU - Zhou,Qiaoling, AU - Lin,Shudian, AU - Wu,Rong, PY - 2010/11/6/entrez PY - 2010/11/6/pubmed PY - 2011/12/13/medline SP - 1048 EP - 56 JF - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JO - Zhong Nan Da Xue Xue Bao Yi Xue Ban VL - 35 IS - 10 N2 - 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). METHODS: We 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. SN - 1672-7347 UR - https://www.unboundmedicine.com/medline/citation/21051829/Fosinopril_and_valsartan_intervention_in_gene_expression_of_Klotho_MMP_9_TIMP_1_and_PAI_1_in_the_kidney_of_spontaneously_hypertensive_rats_ L2 - http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/2010101048.pdf DB - PRIME DP - Unbound Medicine ER -