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Abstract #106497 Published in IGR 23-3
Baicalin prevents fibrosis of human trabecular meshwork cells via inhibiting the MyD88/NF-κB pathway
Li L; Liu Q; Shi L; Zhou X; Wu W; Wang X; Wang L; Wu ZEuropean Journal of Pharmacology 2023; 938: 175425
Trabecular meshwork fibrosis contributes to increased aqueous humor outflow resistance, leading to elevated intraocular pressure in primary open-angle glaucoma. Baicalin, an extract from Scutellaria baicalensis Georgi, has shown anti-fibrotic effects in liver, lung, and kidney diseases. However, its anti-fibrotic effect on human trabecular meshwork (HTM) cells has not yet been clarified. In this study, we investigated its effects on TGF-β2-induced HTM fibrosis as well as the underlying regulatory mechanisms. HTM cells were pretreated with baicalin, TAK-242, and baicalin + TAK-242 for 2 h followed by treatment with or without 5 ng/mL TGF-β2 for 48 h. Cell viability was assayed using cell counting Kit-8 and fibronectin (FN), laminin (LN), and α-smooth muscle actin (α-SMA) were assessed by western blotting, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry. Further, the protein and gene expression levels of the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, and NF-κB p65) were also examined by western blotting and RT-PCR, respectively. Thus, we observed that high doses of baicalin (40 μM) decreased (p < 0.1) HTM cell viability and 20 μM baicalin pretreatment was identified as the optimum pretreatment concentration. TGF-β2 upregulated (p < 0.5) the expression of FN, LN, α-SMA, MyD88, NF-κB p65 proteins and mRNA in HTM cells, and these effects were inhibited by baicalin and TAK-242 (p < 0.5). However, western blot analysis showed that baicalin did not repress TLR4 expression in HTM cells. Therefore, our findings suggested that baicalin could prevent TGF-β2-induced extracellular matrix (FN, LN) deposition and α-SMA expression in HTM cells by inhibiting the MyD88/NF-κB pathway.
Weifang Medical University, Weifang, 261053, China; Senior Department of Ophthalmology, The Third Medical Center of PLA General Hospital, BeiJing, 100039, China; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, 100005, China.
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