Liu Wei, Deng Zhongliang, Zeng Zongyue, Fan Jiaming, Feng Yixiao, Wang Xi, Cao Daigui, Zhang Bo, Yang Lijuan, Liu Bin, Pakvasa Mikhail, Wagstaff William, Wu Xiaoxing, Luo Huaxiu, Zhang Jing, Zhang Meng, He Fang, Mao Yukun, Ding Huiming, Zhang Yongtao, Niu Changchun, Haydon Rex C, Luu Hue H, Wolf Jennifer Moriatis, Lee Michael J, Huang Wei, He Tong-Chuan, Zou Yulong
Departments of Orthopedic Surgery, Breast Surgery, Gastrointestinal Surgery, Obstetrics and Gynecology, and Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
Genes Dis. 2019 Sep 14;7(2):235-244. doi: 10.1016/j.gendis.2019.08.003. eCollection 2020 Jun.
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.
骨形态发生蛋白9（BMP9）（或生长分化因子2，GDF2）最初是从小鼠胎儿肝脏cDNA文库中鉴定出来的。新出现的证据表明，BMP9在出生后发育过程中以及维持组织内稳态方面发挥着多种多效性作用。然而，BMP9信号在发育过程中和/或成年组织中的表达情况仍有待分析。在此，我们对出生后小鼠中BMP9及其信号传导介质的表达情况进行了全面分析。通过分析小鼠ENCODE转录组数据集，我们发现Bmp9在肝脏中高表达，在胚胎脑、成年肺和成年胎盘中可检测到。接下来，我们对从不同年龄段的主要小鼠组织/器官中分离的RNA进行了全面的qPCR分析。我们发现，Bmp9在年轻成年小鼠的肝脏和肺组织中高表达，但在老年小鼠中表达下降。有趣的是，Bmp9在发育中的骨骼中仅以低至中等水平表达。与BMP9相关的TGFβ/BMPR I型受体Alk1在成年肺中高表达。此外，反馈抑制剂Smads Smad6和Smad7在小鼠出生后的组织中广泛表达。然而，BMP信号拮抗剂头蛋白（noggin）在老年组的脂肪和心脏中高表达，在肾脏、肝脏和肺中呈双相表达。因此，我们的研究结果表明，肝脏和肺中产生的循环BMP9可能解释了其对出生后组织/器官的多效性作用，尽管BMP9信号在肝脏和肺中的可能作用仍有待充分了解。
