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The m6A demethylase FTO promotes renal epithelial-mesenchymal transition by reducing the m6A modification of lncRNA GAS5.
Li, Xiaoyan; Li, Yongzhen; Wang, Ying; He, Xiaojie.
Afiliación
  • Li X; Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China; Laboratory of Pediatrics Nephrology, Institute of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.
  • Li Y; Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China; Laboratory of Pediatrics Nephrology, Institute of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.
  • Wang Y; Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China; Laboratory of Pediatrics Nephrology, Institute of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.
  • He X; Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China; Laboratory of Pediatrics Nephrology, Institute of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China. Electronic addre
Cytokine ; 159: 156000, 2022 11.
Article en En | MEDLINE | ID: mdl-36058192
BACKGROUND: Renal interstitial fibrosis (RIF) is the main pathological change of a variety of chronic kidney diseases (CKD). Epigenetic modifications of fibrosis-prone genes regulate RIF progression. This study aimed to investigate long non-coding RNA (lncRNA) N6-methyladenosine (m6A) modification and its role in regulating RIF progression. METHODS: Unilateral ureteral occlusion (UUO) was employed to construct the RIF in vivo model; and TGF-ß1-treated HK-2 and HKC-8 cells were used for in vitro experiments. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The proliferation and migration were evaluated by EdU assay and transwell assay, respectively. In addition, levels of inflammatory cytokines were determined by ELISA assay and qRT-PCR. Moreover, lncRNA GAS5 m6A level was detected using Me-RIP assay. HE and Masson staining were employed to evaluate fibrotic lesions of the kidney. RESULTS: FTO expression was elevated in HK-2 and HKC-8 cells after TGF-ß1 treatment and mouse kidney tissue following UUO, and lncRNA GAS5 was downregulated. LncRNA GAS5 overexpression or FTO silencing suppressed TGF-ß1-induced the increase of EMT-related proteins (Vimentin, Snail and N-cadherin) and inflammatory cytokines (IL-6, IL-1ß and TNF-α) levels in HK-2 cells. FTO suppressed lncRNA GAS5 expression by reducing the m6A modification of lncRNA GAS5. Additionally, FTO knockdown could suppress EMT process and inflammation response induced by TGF-ß1 and UUO in vitro and in vivo. As expected, FTO knockdown abrogated the promotion effects of lncRNA GAS5 silencing on TGF-ß1-induced EMT process and inflammation response in HK-2 and HKC-8 cells. CONCLUSION: FTO promoted EMT process and inflammation response through reducing the m6A modification of lncRNA GAS5.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción Ureteral / Insuficiencia Renal Crónica / ARN Largo no Codificante Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción Ureteral / Insuficiencia Renal Crónica / ARN Largo no Codificante Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido