Mmp15, also known as MT2-MMP, is a member of the membrane-type (MT) MMPs subgroup of matrix metalloproteinases. MMPs are zinc-containing endopeptidases capable of degrading extracellular matrix (ECM) proteins, and Mmp15 is involved in processes like tissue remodeling, cell migration, and invasion by acting on ECM components. It is associated with signaling pathways related to cell-matrix interactions and is of biological importance in various physiological and pathological conditions [1].

In mice, global Mmp15 knockout does not prevent the formation of intact ductal networks during early postnatal mammary gland development, but transcriptome profiling shows it has a key role in regulating mammary gland adipocyte differentiation, specifically controlling the formation of thermogenic brown fat [2]. In medaka, inhibition of Mmp15 expression by gap junction blockers or CDK inhibitors prevents follicle ovulation, indicating its indispensability for this process [3,5]. In Pkd1l1-deficient mice, increased expression of Mmp15 is seen along with fibro-proliferative extrahepatic bile duct transformation and liver fibrosis, suggesting its involvement in the pathophysiology of biliary atresia [4].

In conclusion, Mmp15 plays essential roles in processes such as adipocyte differentiation in the mammary gland, ovulation in medaka, and may be involved in the development of biliary atresia in mouse models. These model-based studies help uncover the function of Mmp15 in specific biological processes and disease-related conditions, providing insights into its biological significance and potential as a therapeutic target in relevant diseases.

References:

1. Pittayapruek, Pavida, Meephansan, Jitlada, Prapapan, Ornicha, Komine, Mayumi, Ohtsuki, Mamitaro. 2016. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. In International journal of molecular sciences, 17, . doi:10.3390/ijms17060868. https://pubmed.ncbi.nlm.nih.gov/27271600/

2. Feinberg, Tamar Y, Rowe, R Grant, Saunders, Thomas L, Weiss, Stephen J. 2016. Functional roles of MMP14 and MMP15 in early postnatal mammary gland development. In Development (Cambridge, England), 143, 3956-3968. doi:. https://pubmed.ncbi.nlm.nih.gov/27633994/

3. Hagiwara, Akane, Ogiwara, Katsueki, Sugama, Natsu, Yamashita, Masakane, Takahashi, Takayuki. 2019. Inhibition of medaka ovulation by gap junction blockers due to its disrupting effect on the transcriptional process of LH-induced Mmp15 expression. In General and comparative endocrinology, 288, 113373. doi:10.1016/j.ygcen.2019.113373. https://pubmed.ncbi.nlm.nih.gov/31874135/

4. Lim, Yi Zou, Zhu, Min, Wang, Yunguan, Zhu, Hao, Corbitt, Natasha. 2024. Pkd1l1-deficiency drives biliary atresia through ciliary dysfunction in biliary epithelial cells. In Journal of hepatology, 81, 62-75. doi:10.1016/j.jhep.2024.02.031. https://pubmed.ncbi.nlm.nih.gov/38460793/

5. Ogiwara, Katsueki, Takahashi, Takayuki. 2019. Nuclear Progestin Receptor Phosphorylation by Cdk9 Is Required for the Expression of Mmp15, a Protease Indispensable for Ovulation in Medaka. In Cells, 8, . doi:10.3390/cells8030215. https://pubmed.ncbi.nlm.nih.gov/30836650/