Nintedanib prevents TGF-β2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells. 2023

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

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.

UI MeSH Term Description Entries
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005353 Fibronectins Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012168 Retinal Pigments Photosensitive protein complexes of varied light absorption properties which are expressed in the PHOTORECEPTOR CELLS. They are OPSINS conjugated with VITAMIN A-based chromophores. Chromophores capture photons of light, leading to the activation of opsins and a biochemical cascade that ultimately excites the photoreceptor cells. Retinal Photoreceptor Pigment,Retinal Pigment,Visual Pigment,Visual Pigments,Retinal Photoreceptor Pigments,Photoreceptor Pigment, Retinal,Photoreceptor Pigments, Retinal,Pigment, Retinal,Pigment, Retinal Photoreceptor,Pigment, Visual,Pigments, Retinal,Pigments, Retinal Photoreceptor,Pigments, Visual
D014746 Vimentin An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.
D015820 Cadherins Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Cadherin,E-Cadherins,Epithelial-Cadherin,Liver Cell Adhesion Molecules,N-Cadherins,Neural Cadherin,P-Cadherins,Uvomorulin,Cadherin-1,Cadherin-2,Cadherin-3,E-Cadherin,Epithelial-Cadherins,Liver Cell Adhesion Molecule,N-Cadherin,Neural Cadherins,P-Cadherin,Placental Cadherins,Cadherin 1,Cadherin 2,Cadherin 3,Cadherin, Neural,Cadherins, Neural,Cadherins, Placental,E Cadherin,E Cadherins,Epithelial Cadherin,Epithelial Cadherins,N Cadherin,N Cadherins,P Cadherin,P Cadherins
D053781 Transforming Growth Factor beta2 A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. TGF-beta2,BSC-1 Cell Growth Inhibitor,Cartilage-Inducing Factor-B,Glioblastoma-Derived T-Cell Suppressor Factor,Polyergin,Suppressor Factor, T-Cell, Glioblastoma-Derived,TGF-beta-2,TGF-beta2 Latency-Associated Protein,TGF-beta2LAP,Transforming Growth Factor beta 2 Latency Associated Peptide,BSC 1 Cell Growth Inhibitor,Cartilage Inducing Factor B,Glioblastoma Derived T Cell Suppressor Factor,Latency-Associated Protein, TGF-beta2,TGF beta2 Latency Associated Protein,TGF beta2LAP
D055213 Retinal Pigment Epithelium The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment. Epithelium, Retinal Pigment,Pigment Epithelium, Retinal

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