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  3. Silibinin attenuates TGF-β2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways

Silibinin attenuates TGF-β2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways

  • Exp Eye Res. 2024 May 22:244:109939. doi: 10.1016/j.exer.2024.109939.
Xueping Wu 1,  Jia Liang 2,  Jinfeng Liu 2,  Yijia Huang 2,  Liyun Zhang 3,  Xin Liu 2,  Junhong Guo 2,  Min Zhang 2,  Yudong Chen 4,  Jiantao Wang 5
Affiliations

Affiliations

  • 1 Jinzhou Medical University, Jinzhou, Liaoning, 121001, China; Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, Guangdong, 518040, China.
  • 2 Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, Guangdong, 518040, China.
  • 3 Department of Ophthalmology, General Hospital of Central Theater Command, Wuhan 430070, P.R. China.
  • 4 The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, Guangdong, 523700, China. Electronic address: doraydc@foxmail.com.
  • 5 Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, Guangdong, 518040, China. Electronic address: wangjiantao65@126.com.
PMID: 38789021 DOI: 10.1016/j.exer.2024.109939
Abstract

Transforming growth factor-β2 (TGF-β2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-β2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-β2-induced cell migration, and mitigated TGF-β2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-β2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as Akt) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-β2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/Akt signaling pathways induced by TGF-β2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-β2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-β2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.

Keywords

Extracellular matrix; Glaucoma; Silibinin; Trabecular meshwork cells; Transforming growth factor-β2.

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