Mxra7, Matrix remodeling associated 7, is a gene related to matrix remodeling processes. It has been implicated in various biological functions and disease-related pathways, playing a crucial role in cell differentiation, hematopoiesis, and immune responses. Genetic models, especially gene knockout mouse models, have been instrumental in uncovering its functions [1,2,3,4,5,6,7,8,9].

In gene knockout studies, Mxra7 -/- mice showed reduced megakaryocytes in bone marrow and spleen, fewer platelets in peripheral blood, and impaired platelet function. Knock-out also inhibited the differentiation of hematopoietic stem/progenitor cells to megakaryocytes, possibly by down-regulating GATA-1 and FOG-1 [1]. In the context of monocyte-to-macrophage differentiation, knockdown of Mxra7 in THP-1 cells affected cell proliferation, adhesion, and differentiation towards M1 macrophages, potentially through NF-κB signaling pathways [2]. In acute promyelocytic leukemia (APL), knockdown of Mxra7 in NB4 cells promoted drug-induced apoptosis and ATRA-induced cell differentiation, while overexpression had opposite effects [3]. In acute B lymphoblastic leukemia cell line REH, knockdown of Mxra7 inhibited cell proliferation and increased sensitivity to cytarabine [4]. In SHI-1 cells, overexpression of Mxra7 reduced drug-induced apoptosis by increasing BCL-2 protein expression [5]. In a CCl4-induced acute liver injury model, Mxra7 deficiency alleviated liver damage, while overexpression aggravated it, potentially by mediating inflammation, immune responses, and matrix remodeling [6]. In cutaneous wound healing, Mxra7 deficiency impaired the process in mice, affecting fibroblast functions through vimentin-related signaling pathways [7]. In psoriasis, MXRA7-deficient mice developed severer psoriasis-like diseases, suggesting it may be a negative modulator in psoriasis development [8]. In bone marrow mesenchymal stem cells (BMSCs), Mxra7-deficient mice showed retarded osteogenesis, and cultured Mxra7-deficient BMSCs had decreased osteogenesis upon induction, while enhanced adipogenesis [9].

In conclusion, Mxra7 plays diverse and essential biological functions in processes such as cell differentiation, hematopoiesis, and wound healing. The use of Mxra7 knockout mouse models has significantly contributed to understanding its role in diseases like platelet-related disorders, leukemia, liver injury, psoriasis, and bone-related conditions, providing potential targets for treatment in these disease areas.

References:

1. Sun, Zhenjiang, Wang, Benfang, Shen, Ying, Wang, Yiqiang, Lin, Dandan. 2023. MXRA7 is involved in megakaryocyte differentiation and platelet production. In Blood science (Baltimore, Md.), 5, 160-169. doi:10.1097/BS9.0000000000000167. https://pubmed.ncbi.nlm.nih.gov/37546710/

2. Sun, Zhenjiang, Ke, Peng, Shen, Ying, Lin, Dandan, Wang, Yiqiang. 2024. MXRA7 is involved in monocyte-to-macrophage differentiation. In Molecular immunology, 171, 12-21. doi:10.1016/j.molimm.2024.05.001. https://pubmed.ncbi.nlm.nih.gov/38735126/

3. Sun, Zhenjiang, Lin, Dandan, Shen, Ying, Wu, Depei, Wang, Yiqiang. 2023. Critical role of MXRA7 in differentiation blockade in human acute promyelocytic leukemia cells. In Experimental hematology, 125-126, 45-54. doi:10.1016/j.exphem.2023.07.001. https://pubmed.ncbi.nlm.nih.gov/37419299/

4. Ma, Kun-Peng, Sun, Zhen-Jiang, Shen, Ying, Wang, Yi-Qiang, Lin, Dan-Dan. . [Effect of MXRA7 on the Biological Functions of Acute B Lymphoblastic Leukemia Cell Line REH]. In Zhongguo shi yan xue ye xue za zhi, 31, 50-56. doi:10.19746/j.cnki.issn.1009-2137.2023.01.008. https://pubmed.ncbi.nlm.nih.gov/36765476/

5. Zheng, Yu-Dan, Sun, Zheng-Jiang, Ma, Kun-Peng, Wang, Yi-Qiang, Lin, Dan-Dan. . [The Effect of Matrix Remodeling Associated 7 (MXRA7) Expression on the Biological Function of SHI-1 Cells]. In Zhongguo shi yan xue ye xue za zhi, 30, 688-694. doi:10.19746/j.cnki.issn.1009-2137.2022.03.005. https://pubmed.ncbi.nlm.nih.gov/35680791/

6. Lin, Dandan, Sun, Zhenjiang, Jin, Ziqi, Shen, Ying, Wang, Yiqiang. 2018. Matrix Remodeling Associated 7 Deficiency Alleviates Carbon Tetrachloride-Induced Acute Liver Injury in Mice. In Frontiers in immunology, 9, 773. doi:10.3389/fimmu.2018.00773. https://pubmed.ncbi.nlm.nih.gov/29720975/

7. Shen, Ying, Ning, Jinling, Zhao, Lu, Yu, Jie, Wang, Yiqiang. 2023. Matrix remodeling associated 7 proteins promote cutaneous wound healing through vimentin in coordinating fibroblast functions. In Inflammation and regeneration, 43, 5. doi:10.1186/s41232-023-00256-8. https://pubmed.ncbi.nlm.nih.gov/36647132/

8. Ning, Jinling, Shen, Ying, Wang, Ting, Chen, Lingling, Wang, Yiqiang. . Altered expression of matrix remodelling associated 7 (MXRA7) in psoriatic epidermis: Evidence for a protective role in the psoriasis imiquimod mouse model. In Experimental dermatology, 27, 1038-1042. doi:10.1111/exd.13687. https://pubmed.ncbi.nlm.nih.gov/29781547/

9. Zhou, Zhishuai, Shen, Ying, Yin, Juanjuan, Chen, Jianquan, Wang, Yiqiang. 2019. Matrix remodeling associated 7 promotes differentiation of bone marrow mesenchymal stem cells toward osteoblasts. In Journal of cellular physiology, 234, 18053-18064. doi:10.1002/jcp.28438. https://pubmed.ncbi.nlm.nih.gov/30843215/