Tyrosine phosphatase Shp2 acts as an antifibrotic regulator in pulmonary fibrosis
作者单位：Department of PathologySir Run Run Shaw HospitalZhejiang University School of Medicine Department of Pathology and Pathophysiology and Program in Molecular Cell BiologyZhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
会议名称：《2017中国长三角遗传学大会》
会议日期：2017年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：pulmonary fibrosis Shp2 mouse model
摘 要：Idiopathic pulmonary fibrosis(IPF) is a chronic interstitial disease of unknown etiology and refractory to current therapeutic options,which is characterized by alveolar inflammation,distorted alveolar architecture and exaggerated collagen ***,the mechanisms underlying this devastating progression remain ***2 is a cytoplasmic tyrosine phosphatase encoded by PTPNll that contains two Src homology(SH2) domains and one catalytic protein tyrosine phosphatase(PTP)***2 integrates multiple signaling pathways involving a variety of physiological ***,little is known about the role of Shp2 in interstitial lung disease,and genetic models have not yet been described Using a combined Cre-loxP-mediated inducible knockout approach,we generated a triple-transgenic Shp2-knockout(SP-C-rtTA/(tetO)7-Cre)/Shp2 f/f) mice in which Shp2 gene was inactivated in alveoli epithelia after Dox *** transgenic mouse model revealed that ablation of Shp2 in alveoli epithelia led to reduced surfactant protein production,impaired alveolar structures and lung mechanics,and eventually the development of spontaneous interstitial ***,selective disruption of Shp2(LysMCre:Shp2) in macrophages augmented IL-4-mediated M2 *** LysMCre:Shp2 mice exhibited normal lung histology at up to 6-8 weeks of age,fibrotic lesions in Shp2-knockout mice were severely aggravated in a bleomycin-induced lung fibrosis *** genetic evidences indicate that Shp2 acts as an anti-fibrotic gene in ***,recent clinical study validate that Shp2 expression is decreased in IPF patients,supporting the pivotal function of Shp2 in *** addition,we have introduced Sftpc-CreETR2/Shp2 mice to further optimize this genetic *** will be administered to induce Cre expression and shp2 gene inactivation in alveoli epithelia which genetic phenotype will be studied in our future *** summary,our findings