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1篇 您的检索式:作者名="Tim Wallis"
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1LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis显示文摘The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang 2024Genes & Diseases2024,11,3:0
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