2. Academic Validation
  3. Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFβ2 through the promotion of fibrotic proteins degradation

Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFβ2 through the promotion of fibrotic proteins degradation

  • Hum Cell. 2024 Oct 22;38(1):4. doi: 10.1007/s13577-024-01141-3.
Gang Wang # 1,  Rumeng Zhao # 1,  Zhenyang Guo # 2,  Huiling Cui 1,  Di Wang 1,  Jing Ren 1,  Shichao Zhu 3,  Ke Zhang 4,  Bo Tang 5,  Jingyi Zhang 1,  Peng Li 6,  Shichao Duan 7,  Haijun Li 8
Affiliations

Affiliations

  • 1 Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China.
  • 2 Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  • 3 Department of Pharmacology, College of Pharmacy, Army Medical University, Chongqing, 400038, China.
  • 4 Henan Medical School, Henan University, Kaifeng, 475001, Henan, China.
  • 5 Huanghe Science and Technology University, Zhengzhou, 450006, Henan, China.
  • 6 Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China. lipeng4754@163.com.
  • 7 Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China. duanshichao@sibcb.ac.cn.
  • 8 Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China. lihaijun@zzu.edu.cn.
  • # Contributed equally.
PMID: 39436499 DOI: 10.1007/s13577-024-01141-3
Abstract

The level of transforming growth factor-beta2 (TGFβ2) is elevated in aqueous humor of partial glaucoma patients, and induced trabecular meshwork (TM) fibrosis, which could cause TM cells dysfunction and lead to intraocular pressure (IOP) elevation. Autophagy is a dynamic process of bulk degradation of organelles and proteins under stress condition, while its functions in fibrotic development remain controversial. Meanwhile, it is still unclear if activation of Autophagy could ameliorate TGFβ2-induced fibrosis in TM cells. In this study, we demonstrated that Autophagy activation with Rapamycin or Everolimus could ameliorate TM fibrosis induced by TGFβ2. We also proved that activation of Autophagy may decrease TM cells fibrosis and reduce elevated IOP induced by TGFβ2 in vivo, while Rapamycin or Everolimus has no effect on TGFβ/SMAD3 pathway activity and fibrotic genes expression. However, when Chloroquine phosphate blocks autophagy-lysosome pathway, the protective effect of Rapamycin or Everolimus on fibrosis was weakened. We established that Autophagy activation ameliorates TM fibrosis through promoting fibrotic proteins degradation.

Keywords

Autophagy; Fibrosis; Rapamycin; Smad3; TGFβ2; Trabecular meshwork cells.

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