Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats
Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats
复制标题
过表达的 C 型利尿钠肽可作为对抗单侧输尿管梗阻大鼠细胞外基质重塑的早期代偿反应
DOI：
10.1007/s11033-012-2186-7
复制
发表时间：
2013-02-01
影响因子：
2.8
通讯作者：
Qin, Yuan Han
中科院分区：
文献类型：
--
作者：
Hu, Peng;Wang, Jing;Qin, Yuan Han
尽管 C 型利钠肽 (CNP) 有益作用的机制尚不完全清楚，但调节基质金属蛋白酶 (MMP)/金属蛋白酶组织抑制剂 (TIMP) 的表达可能发挥重要作用。本文提出的研究旨在首次证明 CNP 对单侧输尿管梗阻 (UUO) 大鼠中 MMPs/TIMPs 表达的调节作用。分别在 UUO 后 3 天、1、2 和 3 个月测定梗阻大鼠肾脏中 CNP、MMP-2、MMP-9、TIMP-1、TIMP-2 和 IV 型胶原 (Col-IV) 表达的连续变化。实时PCR分析显示，梗阻肾脏中CNP、MMP-2和MMP-9 mRNA的表达量较各次相应的SOR显着升高，并随着时间的推移逐渐降低。相反，在 UUO 后 2 个月和 3 个月收集的梗阻肾脏中，与相应的 SOR 组相比，观察到更高的 TIMP-1 和 TIMP-2 mRNA 表达。 CNP、MMP-2、MMP-9、TIMP-1 和 TIMP-2 转录本的上述趋势通过基于免疫组织化学和蛋白质印迹的蛋白表达得到证实，并最终导致整个研究期间梗阻肾脏中 Col-IV 表达逐渐升高。过度表达的 CNP 可能是 UUO 大鼠中对抗细胞外基质重塑的早期代偿反应。
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.