整合素β1信号通路调控结膜松弛症细胞外基质稳态的研究OA

Objective To investigate the regulatory role of the Integrin β1 signaling pathway in maintaining extracel-lular matrix(ECM)homeostasis in conjunctival fibroblasts of conjunctivochalasis(CCH)patients.Methods Conjunctival tissues were collected from 21 CCH patients undergoing surgical treatment(CCH group)and 19 cataract patients scheduled for cataract surgery(NC group)between May 2024 and March 2025.Changes in conjunctival histomorphology,collagen fiber,and elastic fiber were assessed via hematoxylin-eosin,Masson,and Victoria blue staining.The expression of Integrin β1 was detected using immunohistochemistry.Primary conjunctival fibroblasts were cultured using the tissue block adhesion method.Stable Integrin β1-knockdown cells were established.Immunofluorescence,Western blot,and quantitative real-time polymerase chain reaction(qRT-PCR)were used to assess the expression of matrix metalloproteinase(MMP)-2,MMP-9,Collagen I,and proteins and genes related to the Integrin β1/FAK/Akt signaling pathway.Results The CCH group exhibi-ted loosened collagen fibers and disrupted elastic fibers in conjunctival tissue.Compared with the NC group,Integrin β1 ex-pression was significantly reduced in both conjunctival tissue and fibroblasts in the CCH group(both P＜0.01).Western blot and qRT-PCR results demonstrated decreased expression of Integrin β1,Collagen Ⅰ,p-FAK,PI3K,and p-Akt,and concur-rent decreases in the p-FAK/FAK and p-Akt/Akt ratios(all P＜0.05).In addition,MMP-2 and MMP-9 expression increased(both P＜0.05),while the FAK and Akt protein levels remained stable(both P＞0.05).Following transfection with Integrinβ1-shRNA,the activation of the Integrin β1/FAK/Akt signaling pathway was inhibited,MMP-2 and MMP-9 expression in-creased,and Collagen I expression decreased(all P＜0.01).Conclusion Integrin β1 maintains ECM homeostasis by acti-vating the FAK/PI3K/Akt signaling pathway.Its downregulation in CCH reduces Collagen I synthesis and increases MMP-2 and MMP-9 expression,mediating enhanced ECM degradation and thereby contributing to CCH progression.