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Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway.

Authors: Liu, Jia  Yu, Wen  Liu, Yan  Chen, Selena  Huang, Yaqian  Li, Xiaohui  Liu, Cuiping  Zhang, Yanqiu  Li, Zhenzhen  Du, Jie  Tang, Chaoshu  Du, Junbao  Jin, Hongfang 
Citation: Liu J, etal., Sci Rep. 2016 Feb 16;6:21112. doi: 10.1038/srep21112.
Pubmed: (View Article at PubMed) PMID:26880260
DOI: Full-text: DOI:10.1038/srep21112

The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-ß1 (TGF- ß1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- ß1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF-ß1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- ß1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-ß1/Smad2/3 pathway.

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RGD ID: 13504840
Created: 2018-01-29
Species: All species
Last Modified: 2018-01-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.