Timp4, short for Tissue inhibitor of metalloproteinase 4, is a key regulator in the body. It is involved in regulating the activity of matrix metalloproteinases (MMPs), thus playing a crucial role in extracellular matrix (ECM) remodeling. This process is essential for normal physiological functions like tissue development, repair, and maintenance, and is also associated with various disease-related pathways [1-10].

In animal models, the loss of Timp4 did not exacerbate thoracic and abdominal aortic aneurysm severity, as Timp4-/-mice had a similar aneurysm severity to wild-type mice, indicating that Timp4 may not be a major determinant in this aspect [1]. In rats, Timp4-deficiency led to a series of ocular morphology abnormalities in a dose-dependent manner, such as retinal thickness decline, axial length elongation, and changes in sclera collagen, suggesting its importance in ocular development [2]. Also, in the context of atherosclerotic plaque deposition, loss of Timp4 promoted plaque deposition in the abdominal aorta despite suppressed plasma cholesterol levels [3].

In conclusion, Timp4 is vital for maintaining normal physiological functions, especially in ocular development and potentially in vascular health. Gene-knockout mouse models have been instrumental in revealing its role in specific disease conditions like high myopia and atherosclerotic plaque formation. Understanding Timp4's function can offer valuable insights into the underlying mechanisms of these diseases and potentially lead to new therapeutic strategies.

References:

1. Hu, Mei, Meganathan, Ilamaran, Zhu, Jiechun, MacArthur, Rodrick, Kassiri, Zamaneh. 2023. Loss of TIMP3, but not TIMP4, exacerbates thoracic and abdominal aortic aneurysm. In Journal of molecular and cellular cardiology, 184, 61-74. doi:10.1016/j.yjmcc.2023.10.001. https://pubmed.ncbi.nlm.nih.gov/37844423/

2. Zhou, Wenhui, Jiang, Zixuan, Yi, Zhen, Zhang, Qingjiong, Wang, Panfeng. 2023. Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner. In International journal of molecular sciences, 24, . doi:10.3390/ijms242316928. https://pubmed.ncbi.nlm.nih.gov/38069250/

3. Hu, Mei, Jana, Sayantan, Kilic, Tolga, Zhang, Da-Wei, Kassiri, Zamaneh. 2021. Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels. In Arteriosclerosis, thrombosis, and vascular biology, 41, 1874-1889. doi:10.1161/ATVBAHA.120.315522. https://pubmed.ncbi.nlm.nih.gov/33792349/