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 

作者机构：Department of OphthalmologyThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Institute of ImmunologySchool of MedicineZhejiang UniversityHangzhou 310058China Eye Center of the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2023年第15卷第1期

页      面：41-57页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

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) 

主　　题：pterygium autophagy fibrosis SQSTM1 NF-κB 

摘      要：Pterygium is a common ocular disease with a high recurrence rate,characterized by hyperplasia of subconjunctival fibrovascular ***,an important process to maintain cellular homeostasis,participates in the pathogenic fibrosis of different ***,the exact role of autophagy in pterygium pathogenesis remains ***,we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival *** 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 *** autophagic activity was suppressed during TGF-β1-or ultraviolet-induced fibrosis of *** autophagy dramatically retarded the fibrotic progress of ConFB,while blocking autophagy exacerbated this ***,SQSTM1,the main cargo receptor of selective autophagy,was found to significantly promote the fibrosis of ConFB through activating the PKCι-NF-κB signaling *** of SQSTM1,PKCι,or p65 in ConFB delayed TGF-β1-induced *** of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-β1-induced ***,our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1-PKCι-NF-κB signaling *** work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.