TIMP1,即组织金属蛋白酶抑制剂1,是一种重要的调节蛋白质,主要功能是抑制金属蛋白酶(MMPs)的活性,MMPs是一类能够降解细胞外基质(ECM)的酶。TIMP1在多种生理和病理过程中发挥关键作用,包括伤口愈合、炎症反应、肿瘤发生和发展等。
在伤口愈合过程中,TIMP1的表达水平升高,有助于抑制MMPs的过度活性,从而保护新生组织免受破坏。一项研究表明,在人类皮肤伤口的再上皮化过程中,TIMP1的表达显著上调[1]。此外,TIMP1还与炎症性肠病(如溃疡性结肠炎)的发病机制密切相关。研究发现,TIMP1在溃疡性结肠炎患者的肠道黏膜中表达升高,并与炎症细胞浸润相关[2]。在肺癌患者中,TIMP1的表达水平与肿瘤的侵袭性和患者的预后密切相关。研究发现,TIMP1在肺癌组织中的表达水平升高,且与患者的生存期缩短相关[3]。此外,TIMP1在甲状腺乳头状癌(PTC)的发生和发展中也发挥着重要作用。研究表明,PTC患者的FNAB样本中TIMP1的表达水平显著高于良性结节患者[4]。
TIMP1在溃疡性结肠炎相关结直肠癌(UCACRC)的发病机制和预后中扮演着重要角色。研究发现,TIMP1在UCACRC的发生和发展过程中持续高表达,可能是UCACRC预后的潜在生物标志物[5]。此外,TIMP1还与胶质瘤的进展和免疫抑制密切相关。研究表明,TIMP1通过CHI3L1过表达和NF-κB激活促进胶质瘤的发生,并导致免疫抑制性巨噬细胞极化[6]。TIMP1在结直肠癌中的表达与患者的免疫微环境、药物敏感性和铁死亡抑制相关。研究发现,TIMP1在结直肠癌组织中的表达水平升高,并与巨噬细胞和免疫检查点基因的表达相关[7]。此外,TIMP1的表达与铁死亡相关基因的表达呈正相关,提示TIMP1可能参与铁死亡抑制[8]。
综上所述,TIMP1在多种生理和病理过程中发挥着重要作用,包括伤口愈合、炎症反应、肿瘤发生和发展等。TIMP1的表达水平与多种疾病的预后相关,可能是潜在的治疗靶点和生物标志物。进一步研究TIMP1的生物学功能和调控机制,有助于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. Ågren, Magnus S, Litman, Thomas, Eriksen, Jens Ole, Bzorek, Michael, Gjerdrum, Lise Mette Rahbek. 2022. Gene Expression Linked to Reepithelialization of Human Skin Wounds. In International journal of molecular sciences, 23, . doi:10.3390/ijms232415746. https://pubmed.ncbi.nlm.nih.gov/36555389/
2. Pan, Zhaoji, Lin, Hao, Fu, Yanyan, Fang, Jian, Gu, Bing. 2023. Identification of gene signatures associated with ulcerative colitis and the association with immune infiltrates in colon cancer. In Frontiers in immunology, 14, 1086898. doi:10.3389/fimmu.2023.1086898. https://pubmed.ncbi.nlm.nih.gov/36742294/
3. Pietrzak, Jacek, Wosiak, Agnieszka, Szmajda-Krygier, Dagmara, Pązik, Milena, Balcerczak, Ewa. 2023. Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efficacy and Survival of NSCLC Patients. In Biomedicines, 11, . doi:10.3390/biomedicines11071777. https://pubmed.ncbi.nlm.nih.gov/37509417/
4. Dimitrova, Inna, Shinkov, Alexander, Dodova, Rumyana, Kaneva, Radka, Kovatcheva, Roussanka. 2021. Increased gene expression of TIMP1 and CHI3L1 in fine-needle aspiration biopsy samples from papillary thyroid cancer as compared to benign nodules. In Diagnostic cytopathology, 49, 1045-1051. doi:10.1002/dc.24816. https://pubmed.ncbi.nlm.nih.gov/34170085/
5. Huang, Ru, Wang, Kaijing, Gao, Lei, Gao, Wei. 2019. TIMP1 Is A Potential Key Gene Associated With The Pathogenesis And Prognosis Of Ulcerative Colitis-Associated Colorectal Cancer. In OncoTargets and therapy, 12, 8895-8904. doi:10.2147/OTT.S222608. https://pubmed.ncbi.nlm.nih.gov/31802901/
6. Xu, Jianye, Wei, Cheng, Wang, Cong, Zhang, Jianning, Zhang, Shu. 2024. TIMP1/CHI3L1 facilitates glioma progression and immunosuppression via NF-κB activation. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167041. doi:10.1016/j.bbadis.2024.167041. https://pubmed.ncbi.nlm.nih.gov/38290591/
7. Qin, Ya-Fei, Li, Guang-Ming, Wang, Grace, Sun, Da-Qing, Wang, Hao. 2021. Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer. In Therapeutics and clinical risk management, 17, 889-901. doi:10.2147/TCRM.S321101. https://pubmed.ncbi.nlm.nih.gov/34475758/
8. Tilson, M David, Ro, Charles Y. . The candidate gene approach to susceptibility for abdominal aortic aneurysm: TIMP1, HLA-DR-15, ferritin light chain, and collagen XI-Alpha-1. In Annals of the New York Academy of Sciences, 1085, 282-90. doi:. https://pubmed.ncbi.nlm.nih.gov/17182944/