Sun Youqiang, Kuek Vincent, Qiu Heng, Tickner Jennifer, Chen Leilei, Wang Haibin, He Wei, Xu Jiake
The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P. R. China.
Department of Orthopedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P. R. China.
J Cell Physiol. 2018 Mar;233(3):1887-1894. doi: 10.1002/jcp.26013. Epub 2017 Jun 16.
Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading, and survival. NPNT protein belongs to the epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1. Recent studies revealed that NPNT is involved in kidney development, renal injury repair, atrioventricular canal differentiation, pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates osteoblast differentiation and mineralization, as well as osteogenic angiogenesis. Altered expression of NPNT has been linked with the progression of certain types of cancers, such as spontaneous breast tumor metastasis and malignant melanoma. Interestingly, NPNT gene expression can be regulated by a range of external factors such as tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), oncostatin M (OSM), bone morphogenic protein 2 (BMP2), Wnt3a, Vitamin D , and microRNA-378 (miR378). Further understanding the cellular and molecular mechanisms by which NPNT regulates tissue homeostasis in an organ-specific manner is critical in exploring NPNT as a therapeutic target for tissue regeneration and tissue engineering.
肾连蛋白（NPNT）是一种高度保守的细胞外基质蛋白，在调节细胞黏附、分化、铺展和存活中发挥重要作用。NPNT蛋白属于表皮生长因子（EGF）样超家族，并具有几个共同的结构决定簇；包括EGF样重复结构域、MAM结构域（Meprin、A5蛋白和受体蛋白酪氨酸磷酸酶μ）、RGD基序（精氨酸-甘氨酸-天冬氨酸）和一个卷曲螺旋结构域。它通过其RGD基序与整合素α8β1的相互作用来调节整合素介导的信号通路。最近的研究表明，NPNT参与肾脏发育、肾损伤修复、房室管分化、肺功能和肌肉细胞生态位维持。此外，NPNT调节成骨细胞分化和矿化以及成骨血管生成。NPNT表达的改变与某些类型癌症的进展有关，如自发性乳腺肿瘤转移和恶性黑色素瘤。有趣的是，NPNT基因表达可受一系列外部因素调节，如肿瘤坏死因子α（TNF-α）、转化生长因子β（TGF-β）、制瘤素M（OSM）、骨形态发生蛋白2（BMP2）、Wnt3a、维生素D和微小RNA-378（miR378）。进一步了解NPNT以器官特异性方式调节组织稳态的细胞和分子机制对于探索NPNT作为组织再生和组织工程的治疗靶点至关重要。
