Zhi Ren Liu
Georgia State University, USA
Title: EXTRACELLULAR PKM2 FACILITATES WOUND HEALING BY PROMOTING MYOFIBROBLAST DIFFERENTIATION
Biography
Biography: Zhi Ren Liu
Abstract
Injury induced tissue regeneration oft en starts with infl ammation responses. Th e infi ltrated neutrophils and/or macrophages release various diff erent cytokines and growth factors that promotes myofi broblast diff erentiation. Myofi broblast plays a key role in tissue regeneration and reconstruction. However, sustained myofi broblast diff erentiation and survival lead to fi brosis. We report here that infi ltration neutrophils at the wound site release PKM2, a glycolytic enzyme, by its secretive mechanisms during early stages of regeneration. Th e extracellular PKM2 facilitates wound healing by promoting early granulation and angiogenesis. PKM2 facilitates formation of early granulates by promoting fi broblast migration and myofi broblast diff erentiation. Extracellular PKM2 also protects myofubroblasts from apoptosis. We demonstrated that extracellular PKM2 promotes myofi broblast diff erentiation by a TGFβ independent pathway via activation of integrin ï¡vβ3 signaling. Our studies uncovered a novel mechansim of integrin activation. Extracellular PKM2 activates integrin ï¡vβ3 by binding to head open integrin and facilitating a “leg” separation conformation. Our studies reveal a new molecular linker between the early infl ammation response and proliferation phase in tissue regeneration process. Our studies also uncover a novel mechanism of promoting myofi broblast diff erentiation.