Impairment of autophagy promotes human conjunctival fibrosis and pterygium occurrence via enhancing the SQSTM1-NF-κB signaling pathway  

作　　者：Qin He Yiting Cai Jiani Huang Xiaoying He Wei Han Wei Chen 

机构地区：[1]Department of Ophthalmology,The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China [2]Institute of Immunology,School of Medicine,Zhejiang University,Hangzhou 310058,China [3]Eye Center of the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China

出　　处：《Journal of Molecular Cell Biology》2023年第1期41-57,共17页分子细胞生物学报（英文版）

基　　金：supported by the National Natural Science Foundation ofChina(81670842 and 31370879);the China Postdoctoral Science Foundation(2020M671752);the State Natural Science Foundation of Zhejiang Province(LQ20H120006 and LY17C080003);the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(2020kY121).

摘　　要：Pterygium is a common ocular disease with a high recurrence rate,characterized by hyperplasia of subconjunctival fibrovascular tissue.Autophagy,an important process to maintain cellular homeostasis,participates in the pathogenic fibrosis of different organs.However,the exact role of autophagy in pterygium pathogenesis remains unknown.Here,we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues.The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts(ConFB)treated with transforming growth factor-β1(TGF-β1),evidenced by increased fibrotic level and strong proliferative and invasive capabilities.The autophagic activity was suppressed during TGF-β1-or ultraviolet-induced fibrosis of ConFB.Activating autophagy dramatically retarded the fibrotic progress of ConFB,while blocking autophagy exacerbated this process.Furthermore,SQSTM1,the main cargo receptor of selective autophagy,was found to significantly promote the fibrosis of ConFB through activating the PKCι-NF-κB signaling pathway.Knockdown of SQSTM1,PKCι,or p65 in ConFB delayed TGF-β1-induced fibrosis.Overexpression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-β1-induced fibrosis.Collectively,our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1-PKCι-NF-κB signaling cascades.This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.

关 键 词：PTERYGIUM AUTOPHAGY FIBROSIS SQSTM1 NF-κB 

分 类 号：R777.41[医药卫生—眼科]