title: Upregulation of microRNA-205 suppresses vascular endothelial growth factor expression-mediated PI3K/Akt signaling transduction in human keloid fibroblasts.
abstract: Keloid is one of the most frustrating problems related to wounding healing and presents a great challenge in clinic. MicroRNAs (miRs) have shown their potential as a novel therapy for the prevention and treatment of keloid. Vascular endothelial growth factor (VEGF) plays a critical role in the regulation of scar development. In the current study, it was hypothesized that miR-205-5p was capable of suppressing keloid formation by inhibiting the VEGF-mediated wound healing cascade. The expression statuses of miR-205-5p and VEGF in clinical keloid tissues and keloid cell line human keloid fibroblasts (HKF) were detected. Then the direct action of miR-205-5p on VEGF gene was assessed using dual-luciferase assay. Thereafter, orchestrated administrations on HKF with miR-205-5p mimic, specific VEGF siRNA, PI3K agonist (740 Y-P), and PI3K inhibitor (LY294002) were performed to reveal the roles of miR-205-5p and VEGF in keloid formation and further explain the mechanism through which miR-205-5p affected the VEGF-mediated signaling transductions. Our results showed that there was significant low expression of miR-205-5p in keloid tissue specimens and the cell line while the expression of VEGF in keloid tissues was augmented. Moreover, miR-205-5p overexpression dramatically impaired the cell viability, induced the cell apoptosis, and inhibited the cell invasion and migration ability in HKF. Based on the detection of dual luciferase assay and detection at protein level, miR-205-5p antagonized the keloids by directly targeting VEGF expression and subsequently inhibiting PI3K/Akt pathway. The current study is the first one demonstrating that miR-205-5p inhibits the pathogenesis of keloids, indicating the potential of miR-205-5p in the development of therapies for prevention and treatment of keloids.
authors.affiliation: Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Gang
authors.initials: G
authors.lastname: An
authors.affiliation: Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Shuzeng
authors.initials: S
authors.lastname: Liang
authors.affiliation: Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002675:Child, Preschool; D002867:Chromones / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007627:Keloid / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D002867:Chromones; D035683:MicroRNAs; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C533896:MIRN200 microRNA, human; C534425:MIR205, human; C467484:VEGFA protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Akt; Keloid; microRNA-205; vascular endothelial growth factor