RGD Reference Report - Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway. - Rat Genome Database

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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.
RGD ID: 13504840
Pubmed: PMID:26880260   (View Abstract at PubMed)
PMCID: PMC4754767   (View Article at PubMed Central)
DOI: DOI:10.1038/srep21112   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Got1Ratcellular response to mechanical stimulus  IDA mechanical stretchingRGD 
Got1Ratnegative regulation of collagen biosynthetic process  IMP  RGD 
Got1Ratpositive regulation of transforming growth factor beta receptor signaling pathway  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Got1  (glutamic-oxaloacetic transaminase 1)


Additional Information