[대학원 생명과학과 세미나 안내]
연사 : 이상명 교수 (중앙대학교 생명과학과)
연제 : Fibroblast activation by microtubule acetylation in fibrotic diseases
일시 : 2020년 10월 16일 (금) 오후 5시
장소 : 온라인 화상 강의로 진행됩니다.
초청교수 : 김충호 교수
Abstract
Myofbroblasts are the major cell type that is responsible for increase in the mechanical stifness in fbrotic tissues. It haswell documented that the TGF-β/Smad axis is required for myofbroblast diferentiation under the rigid substrate condition. However, the mechanism driving myofbroblast diferentiation in soft substrates remains unknown. In this research,we demonstrated that interaction of yes-associated protein (YAP) and acetylated microtubule via dynein, a microtubulemotor protein drives nuclear localization of YAP in the soft matrix, which in turn increased TGF-β1-induced transcriptionalactivity of Smad for myofbroblast diferentiation. Pharmacological and genetical disruption of dynein impaired the nucleartranslocation of YAP and decreased the TGF-β1-induced Smad activity even though phosphorylation and nuclear localization of Smad occurred normally in α-tubulin acetyltransferase 1 (α-TAT1) knockout cell. Moreover, microtubule acetylationprominently appeared in the fbroblast-like cells nearby the blood vessel in the fbrotic liver induced by CCl4 administration,which was conversely decreased by TGF-β receptor inhibitor. As a result, quantitative inhibition of microtubule acetylationmay be suggested as a new target for overcoming fbrotic diseases.