Mmp12, also known as macrophage metalloelastase, is a matrix metalloproteinase that plays crucial roles in extracellular matrix (ECM) component degradation [3]. It is involved in various biological processes, such as inflammation, angiogenesis, and tissue remodeling, and has been implicated in multiple disease-related pathways [2,3,4,6]. Genetic models, especially gene knockout (KO) mouse models, have been instrumental in studying its functions.

In a mouse model of silicosis, macrophage-derived Mmp12 was found to promote fibrosis by causing sustained damage to endothelial cells, which was accompanied by pro-inflammatory macrophage activation [1]. In a mouse model of subretinal fibrosis, Mmp12 critically contributed to the development of the disease, partially through promoting macrophage-to-myofibroblast transition [2]. In ApcMin/+ mice (a model of colorectal cancer), MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area, indicating its role in cancer cachexia-related weight and muscle loss [5]. Also, in a mouse model mimicking human cardiometabolic diseases, genetic deletion of Mmp12 ameliorated obesity-induced low-grade inflammation, white adipose tissue dysfunction, and atherosclerotic features [6].

In conclusion, Mmp12 is essential in ECM degradation and is involved in multiple biological processes. KO mouse models have revealed its role in diseases like fibrosis, cancer cachexia, and cardiometabolic diseases. Understanding Mmp12's functions through these models may provide potential therapeutic targets for related diseases.

References:

1. Zhou, Xinbei, Zhang, Cong, Yang, Shaoqi, Zhang, Xinxin, Chao, Jie. 2023. Macrophage-derived MMP12 promotes fibrosis through sustained damage to endothelial cells. In Journal of hazardous materials, 461, 132733. doi:10.1016/j.jhazmat.2023.132733. https://pubmed.ncbi.nlm.nih.gov/37816293/

2. Yi, Caijiao, Liu, Jian, Deng, Wen, Chen, Mei, Xu, Heping. 2022. Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis. In Journal of neuroinflammation, 19, 78. doi:10.1186/s12974-022-02433-x. https://pubmed.ncbi.nlm.nih.gov/35382832/

3. Lin, Bingpeng, Ser, Hooi Leng, Wang, Lijing, Lee, Learn-Han, Tan, Loh Teng-Hern. 2023. The Emerging Role of MMP12 in the Oral Environment. In International journal of molecular sciences, 24, . doi:10.3390/ijms24054648. https://pubmed.ncbi.nlm.nih.gov/36902078/

4. Li, Guo-Sheng, Tang, Yu-Xing, Zhang, Wei, Zhou, Hua-Fu, Chen, Gang. . MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma. In Cancer control : journal of the Moffitt Cancer Center, 31, 10732748241235468. doi:10.1177/10732748241235468. https://pubmed.ncbi.nlm.nih.gov/38410859/

5. Jiang, Lingbi, Yang, Mingming, He, Shihui, Wang, Lijing, Li, Jiangchao. 2021. MMP12 knockout prevents weight and muscle loss in tumor-bearing mice. In BMC cancer, 21, 1297. doi:10.1186/s12885-021-09004-y. https://pubmed.ncbi.nlm.nih.gov/34863141/

6. Amor, Melina, Bianco, Valentina, Buerger, Martin, Norata, Giuseppe Danilo, Kratky, Dagmar. 2023. Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice. In Cardiovascular diabetology, 22, 327. doi:10.1186/s12933-023-02064-3. https://pubmed.ncbi.nlm.nih.gov/38017481/