Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism

作     者：Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou 

作者机构：Departments of Orthopedic SurgeryBreast SurgeryGastrointestinal SurgeryObstetrics and Gynecologyand NephrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology LaboratoryDepartment of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Orthopaedic SurgeryThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Ministry of Education Key Laboratory of Diagnostic MedicineThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Laboratory Diagnostic MedicineChongqing General HospitalChongqing 400021China Key Laboratory of Orthopaedic Surgery of Gansu ProvinceThe Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou730030China School of Life SciencesSouthwest UniversityChongqing 400715China Department of Burn and Plastic SurgeryWest China Hospital of Sichuan UniversityChengdu 610041China Department of Orthopaedic SurgeryThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China Department of Orthopaedic SurgeryThe Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430072China Department of Orthopaedic SurgeryBenQ Medical Center Affiliated with Nanjing Medical UniversityNanjing 210000China Department of Orthopaedic SurgeryThe Affiliated Hospital of Qingdao UniversityQingdao 266061China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2020年第7卷第2期

页      面：235-244页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 10[医学] 

基　　金：The reported work was supported in part by research grants from the National Institutes of Health(CA226303 to TCH) the U.S.Department of Defense(OR130096 to JMW) the Scoliosis Research Society(TCH and MJL) This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599) the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.Funding sources were not involved in the study design,in the collection,analysis and interpretation of data in the writing of the report,and in the decision to submit the paper for publication。 

主　　题：BMP9/GDF2 Bone morphogenetic proteins(BMPs) Hepatic metabolism Mesenchymal stem cells Neurogenesis Osteogenic differentiation Pulmonary arterial hypertension Tumorigenesis 

摘      要：Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.