title: Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70.
abstract: Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.
authors.affiliation: Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Burns and Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Burns Surgery, the First Bethune Hospital of Jilin University, Changchun 130021, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Center of Tuberculous Meningitis, Changchun City Hospital for Infectious Diseases, Changchun 130123, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Burns and Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wu
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D057809:HEK293 Cells; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050957:HSP110 Heat-Shock Proteins; C121993:HSPA4 protein, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: HSP70; Let-7c miRNA; dermal fibroblast; heat