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A negative feedback loop centered on SMAD3 expression in transforming growth factor ß1-induced corneal myofibroblast differentiation.
Tang, Yunlan; Du, Enming; Wang, Gang; Qin, Fangyuan; Meng, Zhihong; Dai, Lijuan; Wang, Yiqiang; Ren, Shengwei.
Afiliação
  • Tang Y; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Du E; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Wang G; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Qin F; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Meng Z; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Dai L; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
  • Wang Y; Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China. Electronic address: yiqiang.wang@xjtlu.edu.cn.
  • Ren S; Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China. Electronic address: shengweiren1984@163.com.
Exp Eye Res ; 236: 109654, 2023 11.
Article em En | MEDLINE | ID: mdl-37734427
ABSTRACT
SMAD3 downregulation is documented in transforming growth factor ß1 (TGF-ß1)-induced corneal fibroblasts differentiation to myofibroblasts ("fibroTOmyoDiff") or corneal wound healing. However, the exact regulatory mechanism of TGF-ß1/SMAD3 pathway in this context remains unclear. Here, we investigated the role and related mechanism of SMAD3 down-regulation in TGF-ß1-induced human corneal fibroTOmyoDiff. By detecting expression changes of SMAD family during this process, we demonstrated that SMAD3 protein expression was dramatically decreased in the process and the decrease occurred mainly in SMAD3 gene transcription. Furthermore, SMAD3 overexpression using lentivirus infection and knockdown using sgRNA lentivirus infection or siRNAs revealed that SMAD3 overexpression enhanced TGF-ß1-induced corneal fibroTOmyoDiff and vice versa. In addition, specific siRNAs and inhibitors targeting particular signaling pathway were used to figure out the intracellular signaling pathway regulating SMAD3, and the result showed that the decease of SMAD3 induced by TGF-ß1 stimulation in human corneal fibroblasts (HCFs) was strikingly prevented by SMAD4 knockdown or p38 signaling inhibitor SB203580 treatment. Collectively, these results demonstrate that, in TGF-ß1 induced corneal fibroTOmyoDiff, down-regulation of SMAD3 expression regulated by SMAD4 and p38 signaling pathways forms a negative feedback loop of TGFß signaling to avoid excessive activation of the signaling, which suggest that SMAD3 may be a key target for corneal fibrosis treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Lentivirus / Fator de Crescimento Transformador beta1 Limite: Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Lentivirus / Fator de Crescimento Transformador beta1 Limite: Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China