title: MicroRNA-23b Inhibits the Proliferation and Migration of Heat-Denatured Fibroblasts by Targeting Smad3.
abstract: BACKGROUND
  Skin grafting with the preservation of denatured dermis is a novel strategy for the treatment of burn-injured skin. Denatured dermis has the ability to restore to the morphology and function of normal skin, but the underlying molecular mechanism is elusive. MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development. In this study, we assessed the potential role of miRNA-23b (miR-23b) in the regulation of cell proliferation and migration of heat-denatured fibroblasts and identified the underlying mechanism.
  
  
  METHODS
  The expression of miR-23b in denatured dermis and heat-denatured fibroblasts was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and migration of heat-denatured fibroblasts were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.
  
  
  RESULTS
  miR-23b was downregulated in denatured dermis and heat-denatured fibroblasts. Downregulation of miR-23b dramatically promoted the proliferation and migration of heat-denatured fibroblasts. Subsequent analyses demonstrated that Smad3 was a direct and functional target of miR-23b in heat-denatured fibroblasts, which was validated by the dual luciferase reporter assay. Moreover, immunohistochemistry analysis showed that denatured dermis from rats displayed enhanced staining of Smad3. In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF-β signaling pathways.
  
  
  CONCLUSIONS
  Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns.
authors.affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xipeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Traditional Chinese Medicine, Jinzhou Traditional Chinese Medicine Hospital, Zhangjiajie, Hunan 427000, China.
authors.forename: Jiming
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Pihong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048430:Cell Shape; D020405:Dermis / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051880:Receptors, Notch; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C000590974:MIRN23a microRNA, rat; C552430:MIRN23a microRNA, human