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GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.
Liang, Zun-Hong; Lin, Shi-Shuai; Qiu, Zhi-Yang; Pan, Yun-Chuan; Pan, Nan-Fang; Liu, Yun.
Afiliação
  • Liang ZH; Department of Burn & Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, P.R. China.
  • Lin SS; Department of Burn & Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, P.R. China.
  • Qiu ZY; Department of Burn & Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, P.R. China.
  • Pan YC; Department of Burn & Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, P.R. China.
  • Pan NF; Department of Burn & Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, P.R. China.
  • Liu Y; Department of Plastic and Cosmetic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, P.R. China.
Kaohsiung J Med Sci ; 40(5): 422-434, 2024 May.
Article em En | MEDLINE | ID: mdl-38385859
ABSTRACT
Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cicatrização / MicroRNAs / Reparo do DNA / Fibroblastos / Proteínas Mutadas de Ataxia Telangiectasia Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cicatrização / MicroRNAs / Reparo do DNA / Fibroblastos / Proteínas Mutadas de Ataxia Telangiectasia Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article