Molecular structure and function of microfibrillar‐associated proteins in skeletal and metabolic disorders and cancers. Issue 1 (22nd June 2020)

• Record Type: Journal Article
• Authors: Zhu, Sipin; Ye, Lin; Bennett, Samuel; Xu, Huazi; He, Dengwei; Xu, Jiake
• Is Part Of: Journal of cellular physiology. Volume 236:Issue 1(2021)
• Page Start: 41
• Page End: 48
• Publication Date: 2020-06-22
• Subjects: bone -- connective tissue -- enzyme -- fibre -- genotype -- osteoclast -- phenotype; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29893
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Microfibrillar‐associated proteins (MFAPs) are integral extracellular matix glycoproteins that play diverse roles in the tropism of tissues. We review the molecular structures and distinct functions of five subfamily members (MFAP1‐5). Understanding the tissue‐specific pathophysiology of MFAPs might uncover novel therapeutic interventions for related diseases.