title: MiRNA-21 promotes fibrosis in orbital fibroblasts from thyroid-associated ophthalmopathy.
abstract: OBJECTIVE
  This study aimed to determine the role of miR-21 in orbital fibroblasts obtained from donors with thyroid-associated ophthalmopathy (TAO) and to elucidate the regulation of fibrosis by miR-21 in the pathological process of TAO.
  
  
  METHODS
  The expression of miR-21 was investigated in orbital tissues from 26 donors with TAO and 10 donors without TAO. Human orbital fibroblasts were cultivated from TAO donors, and the role of miR-21 in orbital fibroblast proliferation, apoptosis, and differentiation was analyzed. Moreover, the effect of transforming growth factor-beta1 (TGF-β1) on miR-21 expression was also analyzed. In addition, the regulation of miR-21 in TGF-β1-induced collagen production was determined.
  
  
  RESULTS
  The expression of miR-21 in orbital fibroblasts from TAO was higher than in donors without TAO. Additional experiments demonstrated that miR-21 enhanced proliferation, decreased apoptosis, and promoted differentiation in TAO orbital fibroblasts. Moreover, this study also showed that TGF-β1 induced miR-21 expression in a time- and dose-dependent manner and miR-21 promoted collagen I mRNA expression and total collagen production induced by TGF-β1. Additionally, miR-21 activated the TGF-β1/Smad signaling pathway by enhancing Smad3 phosphorylation.
  
  
  CONCLUSIONS
  The present study shows that miR-21 regulates cell proliferation, apoptosis, and differentiation in orbital fibroblasts from TAO, and acts as a mediator in TGF-β1-induced collagen production. These data predict a close association between miR-21 and orbital muscle fibrosis, and provide a novel therapeutic target for TAO.
authors: Department of Ophthalmology and Eye Research Center, Hunan, China.
authors: Bo-ding
authors: BD
authors: Tong
authors: Department of Ophthalmology and Eye Research Center, Hunan, China.
authors: Man-Yi
authors: MY
authors: Xiao
authors: Department of Ophthalmology and Eye Research Center, Hunan, China.
authors: Jie-Xi
authors: JX
authors: Zeng
authors: Department of Ophthalmology and Eye Research Center, Hunan, China.
authors: Wei
authors: W
authors: Xiong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D049970:Graves Ophthalmopathy / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009915:Orbit / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D012516:Osteosarcoma / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010766:Phosphorylation; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1