Nintedanib prevents TGF-β2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells

Yiwei Yin; Shikun Liu; Li Pu; Jing Luo; Hanhan Liu; Wenyi Wu

Biomedicine & Pharmacotherapy (May 2023)

Nintedanib prevents TGF-β2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells

Yiwei Yin,
Shikun Liu,
Li Pu,
Jing Luo,
Hanhan Liu,
Wenyi Wu

Affiliations

Yiwei Yin: Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, China; Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
Shikun Liu: Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, China
Li Pu: Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
Jing Luo: Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China
Hanhan Liu: Department of Ophthalmology, Third Xiangya Hospital, Central South University, Changsha, China; Correspondence to: 135 Tongzipo street, yuelu, Changsha, Hunan, China.
Wenyi Wu: Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China; Correspondence to: 87 xiangya street, Kaifu, Changsha, Hunan, China.

Journal volume & issue: Vol. 161
p. 114543

Abstract

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Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 μM nintedanib was added to 20 ng/mL transforming growth factor beta 2 (TGF-β2)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 μM nintedanib suppressed TGF-β2-induced E-cadherin expression decreased and Fibronectin, N-cadherin, Vimentin, and α-SMA expression increased. Quantitative real-time PCR results showed that 1 μM nintedanib decreased TGF-β2-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-β2-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 μM nintedanib ameliorated TGF-β2-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-β2-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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