Diabetes-induced loss of gastric ICC accompanied by up-regulation of natriuretic peptide signaling pathways in STZ-induced diabetic mice
Diabetes-induced loss of gastric ICC accompanied by up-regulation of natriuretic peptide signaling pathways in STZ-induced diabetic mice
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STZ 诱导的糖尿病小鼠中糖尿病诱导的胃 ICC 丧失伴随利尿钠肽信号通路上调
DOI：
10.1016/j.peptides.2012.12.024
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发表时间：
2013-02-01
期刊：
影响因子：
3
通讯作者：
Xu, Wen-Xie
中科院分区：
文献类型：
--
作者：
Wu, Yi-Song;Lu, Hong-Li;Xu, Wen-Xie
我们的前期研究表明，利钠肽（NPs）在调节胃平滑肌运动中起抑制作用。然而，目前尚不清楚纳米颗粒是否参与糖尿病诱导的胃Cajal间质细胞（ICC）的损失。本研究旨在探讨糖尿病小鼠胃ICC丢失与利钠肽信号通路的关系。结果显示，STZ诱导的糖尿病小鼠胃平滑肌细胞c-Kit和膜结合干细胞因子（mSCF）蛋白表达水平降低。而糖尿病小鼠同一部位的利钠肽受体（NPR）-A、B和C的mRNA和蛋白表达水平均升高。C型利钠肽（CNP）呈剂量依赖性地抑制糖尿病小鼠胃窦平滑肌的自发收缩幅度，并增强其抑制作用。不同浓度CNP预处理胃平滑肌细胞可显著降低mSCF表达水平。8-溴鸟苷-3 '，5'-环单磷酸（8-Br-cGMP）是一种膜渗透性cGMP类似物，可模拟CNP的作用，但不能模拟cANF（一种特异性NPR-C激动剂）的作用。四甲基偶氮唑盐（MTT）法显示，高浓度cANF（10（-6）mol/L）抑制GSMCs增殖。提示NPs/NPR-A、B/cGMP和NPs/NPR-C信号通路的上调可能参与了糖尿病引起的胃ICC丢失。(C)2012 Elsevier Inc. All rights reserved.
Our previous study demonstrated that natriuretic peptides (NPs) play an inhibitory role in regulation of gastric smooth muscle motility. However, it is not clear whether NPs are involved in diabetics-induced loss of gastric interstitial cell of Cajal (ICC). The present study was designed to investigate the relationship between diabetics-induced loss of gastric ICC and natriuretic peptide signaling pathway in streptozotocin (STZ)-induced diabetic mice. The results showed that the protein expression levels of c-Kit and membrane-bound stem cell factor (mSCF) in gastric smooth muscle layers were decreased in STZ-induced diabetic mice. However, both mRNA and protein expression levels of natriuretic peptide receptor (NPR)-A, B and C were increased in the same place of the diabetic mice. The amplitude of spontaneous contraction in gastric antral smooth muscles was inhibited by C-type natriuretic peptide (CNP) dose-dependently and the inhibitory effect was potentiated in diabetic mice. Pretreatment of the cultured gastric smooth muscle cells (GSMCs) with different concentration of CNP can significantly decrease the mSCF expression level. 8-Bromoguanosine-3',5'-cyclomo-nophosphate (8-Br-cGMP), a membrane permeable cGMP analog, mimicked the effect of CNP but not cANF (a specific NPR-C agonist). Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay showed that high concentration of cANF (10(-6) mol/L) inhibited cell proliferation in cultured GSMCs. These findings suggest that up-regulation of NPs/NPR-A, B/cGMP and NPs/NPR-C signaling pathways may be involved in diabetes-induced loss of gastric ICC. (C) 2012 Elsevier Inc. All rights reserved.