Molecular structure and function of microfibrillar-associated proteins in skeletal and metabolic disorders and cancers.,Journal of Cellular Physiology

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Molecular structure and function of microfibrillar-associated proteins in skeletal and metabolic disorders and cancers.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-06-22 , DOI: 10.1002/jcp.29893
Sipin Zhu _{1,

2} , Lin Ye ₃ , Samuel Bennett ₂ , Huazi Xu ₁ , Dengwei He ₃ , Jiake Xu _{1,

2}

Affiliation

Microfibrillar‐associated proteins (MFAPs) are extracellular matrix glycoproteins, which play a role in microfibril assembly, elastinogenesis, and tissue homeostasis. MFAPs consist of five subfamily members, including MFAP1, MFAP2, MFAP3, MFAP4, and MFAP5. Among these, MFAP2 and MFAP5 are most closely related, and exhibit very limited amino acid sequence homology with MFAP1, MFAP3, and MFAP4. Gene expression profiling analysis reveals that MFAP2, MFAP5, and MFAP4 are specifically expressed in osteoblastic like cells, whereas MFAP1 and MFAP3 are more ubiquitously expressed, indicative of their diverse role in the tropism of tissues. Molecular structural analysis shows that each MFAP family member has distinct features, and functional evidence reveals discrete purposes of individual MFAPs. Animal studies indicate that MFAP2‐deficient mice exhibit progressive osteopenia with elevated receptor activator of NF‐κB ligand (RANKL) expression, whereas MFAP5‐deficient mice are neutropenic, and MFAP4‐deficient mice displayed emphysema‐like pathology and the impaired formation of neointimal hyperplasia. Emerging data also suggest that MFAPs are involved in cancer progression and fat metabolism. Further understanding of tissue‐specific pathophysiology of MFAPs might offer potential novel therapeutic targets for related diseases, such as skeletal and metabolic disorders, and cancers.

中文翻译：

微纤维相关蛋白在骨骼和代谢疾病和癌症中的分子结构和功能。

微纤维相关蛋白 (MFAP) 是细胞外基质糖蛋白，在微纤维组装、弹性蛋白生成和组织稳态中发挥作用。MFAPs由五个亚家族成员组成，包括MFAP1、MFAP2、MFAP3、MFAP4和MFAP5。其中，MFAP2和MFAP5的亲缘关系最密切，与MFAP1、MFAP3和MFAP4的氨基酸序列同源性非常有限。基因表达谱分析显示 MFAP2、MFAP5 和 MFAP4 在成骨细胞样细胞中特异性表达，而 MFAP1 和 MFAP3 更普遍表达，表明它们在组织趋向性中的不同作用。分子结构分析表明，每个 MFAP 家族成员都有不同的特征，功能证据揭示了单个 MFAP 的不同目的。动物研究表明，MFAP2 缺陷小鼠表现出渐进性骨质减少，NF-κB 配体受体激活剂 (RANKL) 表达升高，而 MFAP5 缺陷小鼠中性粒细胞减少，MFAP4 缺陷小鼠表现出肺气肿样病理和新生内膜增生受损. 新兴数据还表明 MFAPs 参与癌症进展和脂肪代谢。进一步了解 MFAP 的组织特异性病理生理学可能为相关疾病（如骨骼和代谢紊乱以及癌症）提供潜在的新治疗靶点。新兴数据还表明 MFAPs 参与癌症进展和脂肪代谢。进一步了解 MFAP 的组织特异性病理生理学可能为相关疾病（如骨骼和代谢紊乱以及癌症）提供潜在的新治疗靶点。新兴数据还表明 MFAPs 参与癌症进展和脂肪代谢。进一步了解 MFAP 的组织特异性病理生理学可能为相关疾病（如骨骼和代谢紊乱以及癌症）提供潜在的新治疗靶点。

更新日期：2020-06-23

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