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Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats

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Abstract

Although the mechanism underlying C-type natriuretic peptide (CNP) beneficial effects is not entirely understood, modulating the expression of matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) may play an important role. The study presented herein was designed as a first demonstration of the regulative effects of CNP on MMPs/TIMPs expression in unilateral ureteral obstruction (UUO) rats. The continuous changes of CNP, MMP-2, MMP-9, TIMP-1, TIMP-2 and type IV collagen (Col-IV) expression were determined in the obstructed rat kidneys at 3 days, 1, 2, and 3 months post-UUO respectively. According to the real-time PCR analysis, CNP, MMP-2 and MMP-9 mRNA expression in the obstructed kidneys were significantly higher compared to every time corresponding SOR, and progressively decreased over time. In contrast, in the obstructed kidneys collected 2 and 3 months post-UUO, the higher TIMP-1 and TIMP-2 mRNA expression were observed in comparison to the corresponding SOR group. The above trends of CNP, MMP-2, MMP-9, TIMP-1, and TIMP-2 transcripts were confirmed by their protein expression based on immunohistochemistry and western blot, and finally contributed to the progressive elevated Col-IV expression in the obstructed kidneys throughout the entire study period. Overexpressed CNP may be an early compensatory response to counteract extracellular matrix remodeling in UUO rats.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81000306) and the Post-Doctoral Foundation of Anhui Medical University (No. 2009KJ02).

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei, 230022, People’s Republic of China

    Peng Hu, Jing Wang, Xue Qi Zhao, Bo Hu & Ling Lu

  2. Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuang-Yong Road, Nanning, 530021, People’s Republic of China

    Yuan Han Qin

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  1. Peng Hu
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Correspondence to Peng Hu.

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Hu, P., Wang, J., Zhao, X.Q. et al. Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats. Mol Biol Rep 40, 1429–1441 (2013). https://doi.org/10.1007/s11033-012-2186-7

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  • DOI: https://doi.org/10.1007/s11033-012-2186-7

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