Mmp2(基质金属蛋白酶-2)是一种在多种生物学过程中发挥重要作用的酶,它属于基质金属蛋白酶(MMPs)家族。MMPs是一类锌离子依赖性内肽酶,主要负责降解细胞外基质(ECM)和基底膜,从而在组织重塑、伤口愈合、发育、血管生成和肿瘤侵袭等过程中发挥关键作用。Mmp2的表达和活性受到多种因素的调控,包括基因多态性、转录因子、表观遗传修饰和微小RNA等。
Mmp2在生殖系统中也发挥重要作用,它与胚胎植入和胎盘形成密切相关。有研究表明,Mmp2基因的某些单核苷酸多态性(SNPs)与复发性自发性流产(RSA)的风险增加相关[1]。Mmp2的-735T等位基因和Mmp9的-1562T等位基因与RSA风险显著相关。此外,Mmp2基因的表达受到转录因子scleraxis的调控,scleraxis直接激活Mmp2基因启动子,导致组蛋白乙酰化增加,进而促进Mmp2的表达[2]。
Mmp2还在心血管系统中发挥重要作用,它参与心脏细胞外基质的重塑,影响心脏功能。研究发现,Mmp2基因的某些SNPs与下肢浅表静脉曲张的发生相关[3]。此外,Mmp2基因的表达还受到微小RNA-4443的调控,miR-4443通过直接抑制Mmp2的表达,抑制滋养层的迁移和侵袭,进而影响子痫前期(PE)的发生和发展[4]。
Mmp2还与多种肿瘤的发生和发展密切相关。有研究表明,Mmp2基因的某些SNPs与前列腺癌、膀胱癌和胶质瘤的易感性增加相关[5,6,7]。此外,Mmp2的表达和活性受到DNA甲基转移酶3b(DNMT3b)的调控,DNMT3b通过下调Mmp2的表达和活性,抑制肿瘤的发生和发展[8]。
Mmp2还与肌肉生长和发育相关。研究发现,Mmp2基因的某些SNPs与猪的长肌面积相关[9]。此外,Mmp2基因的某些SNPs还与子宫内膜异位症的易感性增加相关[10]。
综上所述,Mmp2是一种重要的酶,参与多种生物学过程,包括生殖、心血管、肿瘤和肌肉生长等。Mmp2的表达和活性受到多种因素的调控,包括基因多态性、转录因子、表观遗传修饰和微小RNA等。Mmp2的研究有助于深入理解其在各种生物学过程中的作用机制,为相关疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Yan, Yang, Fang, Lanlan, Li, Yuxi, Cheng, Jung-Chien, Sun, Ying-Pu. 2020. Association of MMP2 and MMP9 gene polymorphisms with the recurrent spontaneous abortion: A meta-analysis. In Gene, 767, 145173. doi:10.1016/j.gene.2020.145173. https://pubmed.ncbi.nlm.nih.gov/33007375/
2. Nagalingam, Raghu S, Safi, Hamza A, Al-Hattab, Danah S, Wigle, Jeffrey T, Czubryt, Michael P. 2018. Regulation of cardiac fibroblast MMP2 gene expression by scleraxis. In Journal of molecular and cellular cardiology, 120, 64-73. doi:10.1016/j.yjmcc.2018.05.004. https://pubmed.ncbi.nlm.nih.gov/29750994/
3. Görmüş, Uzay, Kahraman, Ozlem Timirci, Isbir, Selim, Tekeli, Atike, Isbir, Turgay. . MMP2 gene polymorphisms and MMP2 mRNA levels in patients with superficial varices of lower extremities. In In vivo (Athens, Greece), 25, 387-91. doi:. https://pubmed.ncbi.nlm.nih.gov/21576412/
4. Chen, Chao, Gao, Jing, Chen, Dan, Yang, Xingyu, Cheng, Weiwei. 2022. miR-4443/MMP2 suppresses the migration and invasion of trophoblasts through the HB-EGF/EGFR pathway in preeclampsia. In Cell cycle (Georgetown, Tex.), 21, 2517-2532. doi:10.1080/15384101.2022.2103897. https://pubmed.ncbi.nlm.nih.gov/35899982/
5. Costa, Angela Margarida, Pinto, Filipe, Martinho, Olga, Jordan, Peter, Reis, Rui Manuel. . Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas. In Oncotarget, 6, 1422-34. doi:. https://pubmed.ncbi.nlm.nih.gov/25596741/
6. Zhang, Kaiping, Chen, Xianguo, Zhou, Jun, Zhang, Li, Liang, Chaozhao. . Association between MMP2-1306 C/T polymorphism and prostate cancer susceptibility: a meta-analysis based on 3906 subjects. In Oncotarget, 8, 45020-45029. doi:10.18632/oncotarget.16972. https://pubmed.ncbi.nlm.nih.gov/28445160/
7. Dofara, SuÉlÈne Georgina, Chang, Sue-Ling, Diorio, Caroline. . Gene Polymorphisms and Circulating Levels of MMP-2 and MMP-9: A Review of Their Role in Breast Cancer Risk. In Anticancer research, 40, 3619-3631. doi:10.21873/anticanres.14351. https://pubmed.ncbi.nlm.nih.gov/32620601/
8. Peres, Rafael, Furuya, Hideki, Pagano, Ian, Hokutan, Kanani, Rosser, Charles J. . Angiogenin contributes to bladder cancer tumorigenesis by DNMT3b-mediated MMP2 activation. In Oncotarget, 7, 43109-43123. doi:10.18632/oncotarget.10097. https://pubmed.ncbi.nlm.nih.gov/27317771/
9. Onteru, S K, Fan, B, Rothschild, M F. . The MMP2 gene may be associated with longissimus dorsi muscle area in the pig (Sus scrofa). In Journal of applied genetics, 50, 251-2. doi:10.1007/BF03195679. https://pubmed.ncbi.nlm.nih.gov/19638680/
10. Tsai, Eing-Mei, Wang, Yung-Song, Lin, Chang-Shen, Wu, Ming-Tsang, Juo, Suh-Hang H. 2013. A microRNA-520 mirSNP at the MMP2 gene influences susceptibility to endometriosis in Chinese women. In Journal of human genetics, 58, 202-9. doi:10.1038/jhg.2013.1. https://pubmed.ncbi.nlm.nih.gov/23364396/