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The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis.
Amino Acids. 2014 Dec; 46(12):2693-704.AA

Abstract

Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is a key event in renal interstitial fibrosis and the progression of chronic kidney disease (CKD). Apelin is a regulatory peptide involved in the regulation of normal renal hemodynamics and tubular functions, but its role in renal fibrosis remains unknown. In this study, we examined the inhibitory effects of apelin on transforming growth factor-β1 (TGF-β1)-induced EMT in HK-2 cells, and evaluated its therapeutic efficacy in mice with complete unilateral ureteral obstruction (UUO). In vitro, apelin inhibited TGF-β1-mediated upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin. Increased levels of phosphorylated Smad-2/3 and decreased levels of Smad7 in TGF-β1-stimulated cells were reversed by apelin co-treatment. In the UUO model, administration of apelin significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin and laminin expression, and markedly suppressed expression of α-SMA, TGF-β1 and its type I receptor, as well as interstitial matrix components. Interestingly, in UUO mice, there was a reduction in the plasma level of apelin, which was compensated by upregulation of APJ expression in the injured kidney. Exogenous supplementation of apelin normalized the level of plasmatic apelin and renal APJ. In conclusion, our study provides the first evidence that apelin is able to ameliorate renal interstitial fibrosis by suppression of tubular EMT through a Smad-dependent mechanism. The apelinergic system itself may promote some compensatory response in the renal fibrotic process. These results suggest that apelin has potential renoprotective effects and may be an effective agent for retarding CKD progression.

Authors+Show Affiliations

Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Xi Cheng District, Beijing, 100050, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25164121

Citation

Wang, Li-Yan, et al. "The Regulatory Peptide Apelin: a Novel Inhibitor of Renal Interstitial Fibrosis." Amino Acids, vol. 46, no. 12, 2014, pp. 2693-704.
Wang LY, Diao ZL, Zhang DL, et al. The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis. Amino Acids. 2014;46(12):2693-704.
Wang, L. Y., Diao, Z. L., Zhang, D. L., Zheng, J. F., Zhang, Q. D., Ding, J. X., & Liu, W. H. (2014). The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis. Amino Acids, 46(12), 2693-704. https://doi.org/10.1007/s00726-014-1826-8
Wang LY, et al. The Regulatory Peptide Apelin: a Novel Inhibitor of Renal Interstitial Fibrosis. Amino Acids. 2014;46(12):2693-704. PubMed PMID: 25164121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis. AU - Wang,Li-Yan, AU - Diao,Zong-Li, AU - Zhang,Dong-Liang, AU - Zheng,Jun-Fang, AU - Zhang,Qi-Dong, AU - Ding,Jia-Xiang, AU - Liu,Wen-Hu, Y1 - 2014/08/28/ PY - 2014/05/23/received PY - 2014/08/14/accepted PY - 2014/8/29/entrez PY - 2014/8/29/pubmed PY - 2015/7/22/medline SP - 2693 EP - 704 JF - Amino acids JO - Amino Acids VL - 46 IS - 12 N2 - Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is a key event in renal interstitial fibrosis and the progression of chronic kidney disease (CKD). Apelin is a regulatory peptide involved in the regulation of normal renal hemodynamics and tubular functions, but its role in renal fibrosis remains unknown. In this study, we examined the inhibitory effects of apelin on transforming growth factor-β1 (TGF-β1)-induced EMT in HK-2 cells, and evaluated its therapeutic efficacy in mice with complete unilateral ureteral obstruction (UUO). In vitro, apelin inhibited TGF-β1-mediated upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin. Increased levels of phosphorylated Smad-2/3 and decreased levels of Smad7 in TGF-β1-stimulated cells were reversed by apelin co-treatment. In the UUO model, administration of apelin significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin and laminin expression, and markedly suppressed expression of α-SMA, TGF-β1 and its type I receptor, as well as interstitial matrix components. Interestingly, in UUO mice, there was a reduction in the plasma level of apelin, which was compensated by upregulation of APJ expression in the injured kidney. Exogenous supplementation of apelin normalized the level of plasmatic apelin and renal APJ. In conclusion, our study provides the first evidence that apelin is able to ameliorate renal interstitial fibrosis by suppression of tubular EMT through a Smad-dependent mechanism. The apelinergic system itself may promote some compensatory response in the renal fibrotic process. These results suggest that apelin has potential renoprotective effects and may be an effective agent for retarding CKD progression. SN - 1438-2199 UR - https://www.unboundmedicine.com/medline/citation/25164121/The_regulatory_peptide_apelin:_a_novel_inhibitor_of_renal_interstitial_fibrosis_ L2 - https://dx.doi.org/10.1007/s00726-014-1826-8 DB - PRIME DP - Unbound Medicine ER -