Mmp10-flox Mouse

Mmp10, also known as Stromelysin-2, is a matrix metalloproteinase. It is involved in multiple biological processes, such as the immune response, and is associated with pathways like PPARγ-STAT3, Wnt/β-catenin, and NF-κB signaling. Genetic models, like KO mouse models, have been crucial in understanding its functions [1,2,6,7,8].

In a NASH model, Mmp10-KO and Mmp10-OE mice studies showed that Mmp10 is downregulated in NASH. Overexpression of Mmp10 alleviates hepatic steatosis and inflammation by regulating macrophage M2 polarization through the PPARγ-STAT3 pathway [1]. In a TLR7-mediated tolerance model, Mmp10-/-mice failed to develop immune tolerance to TLR7 ligand, indicating Mmp10 is essential for this process [2]. In tongue cancer, MMP10 knockdown in mice suppressed nodal metastases [3]. For ischemic stroke, rs17860949 polymorphism in Mmp10 was associated with a reduced risk in the Chinese Han population [4]. In a diabetic murine model of ischemic stroke, MMP10 treatment was more effective than tPA in reducing infarct size and neurodegeneration [5]. In tracheal fibrosis, SOX9 promotes ECM deposition by increasing MMP10 expression, and SOX9 knockdown in vivo ameliorated tracheal fibrosis [6]. In colitis and CAC models, miR-148/152 family deficiency in mice elevated MMP10, disrupting the intestinal barrier and activating NF-κB signaling [7]. In a Pseudomonas aeruginosa infection model, Mmp10-/-mice had increased morbidity, and adoptive transfer of wild-type macrophages normalized the condition, showing MMP10's role in moderating the pro-inflammatory response of macrophages [8]. In NSCLC, MMP10 knockdown in A549 cells initiated radiosensitization, as MMP10 is involved in DNA damage repair post-ionizing radiation [9]. In oral squamous cell carcinoma, MMP10 expression increased with nodal level, suggesting its role as a prognostic indicator [10].

In conclusion, Mmp10 plays diverse and significant roles in multiple disease conditions including NASH, immune tolerance, cancer metastasis, ischemic stroke, tracheal fibrosis, colitis, and NSCLC. The use of KO mouse models has been instrumental in revealing these functions, providing insights into potential therapeutic targets for these diseases.