Cthrc1-KO Mouse

Cthrc1, or Collagen Triple Helix Repeat Containing 1, is a secreted glycoprotein. It plays a pivotal role in extracellular matrix (ECM) deposition, wound repair, and tissue remodeling, and is closely associated with TGF-β and canonical Wnt signaling pathways [1,2,3,4]. It is involved in multiple physiological processes such as metabolism, arterial remodeling, bone formation, and peripheral nervous system myelination [3]. Genetic models, like gene knockout (KO) mouse models, are valuable for studying its functions.

In liver fibrosis models, Cthrc1 -/- mice showed attenuated carbon tetrachloride (CCl4) or thioacetamide (TAA)-induced liver fibrosis compared to control mice. Cthrc1 promoted hepatic stellate cells (HSCs) transformation to an activated state and enhanced their migratory or contractile capacities via TGF-β signaling [2]. In myocardial infarction (MI) models, Cthrc1 deficiency in mice aggravated cardiac function, reduced collagen deposition, increased mortality due to cardiac rupture, and affected the levels of related proteins such as CD31, α-smooth muscle actin, collagen I, collagen III, matrix metalloproteinase 2, and matrix metalloproteinase 9. These effects could be partly reversed by rCthrc1 or rWNT5A protein, indicating Cthrc1's role in wound repair and preventing cardiac rupture after MI via the non-canonical WNT5A-PCP signaling pathway [5].

In conclusion, Cthrc1 is crucial for ECM-related functions, tissue repair, and remodeling. KO mouse models have revealed its significance in liver fibrosis and post-myocardial infarction wound repair. These findings contribute to understanding the molecular mechanisms underlying these disease conditions, potentially providing new targets for therapeutic interventions.

References:

1. Mukhatayev, Zhussipbek, Adilbayeva, Altynay, Kunz, Jeannette. 2024. CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis. In Cells, 13, . doi:10.3390/cells13110946. https://pubmed.ncbi.nlm.nih.gov/38891078/

2. Li, Jun, Wang, Yahui, Ma, Mingze, Xu, Qing, Zhang, Zhigang. 2019. Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-β signaling. In EBioMedicine, 40, 43-55. doi:10.1016/j.ebiom.2019.01.009. https://pubmed.ncbi.nlm.nih.gov/30639416/

3. Liu, Ya-Juan, Du, Jing, Li, Jie, Tan, Xiao-Ping, Zhang, Qing. 2023. CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review). In Oncology letters, 25, 266. doi:10.3892/ol.2023.13852. https://pubmed.ncbi.nlm.nih.gov/37216164/

4. Cao, Mingzhen, Ke, Da, Zhou, Heng. 2024. The role and molecular mechanism of CTHRC1 in fibrosis. In Life sciences, 350, 122745. doi:10.1016/j.lfs.2024.122745. https://pubmed.ncbi.nlm.nih.gov/38834096/

5. Wang, Di, Zhang, Yaping, Ye, Tianbao, Jin, Xian, Shen, Chengxing. 2023. Cthrc1 deficiency aggravates wound healing and promotes cardiac rupture after myocardial infarction via non-canonical WNT5A signaling pathway. In International journal of biological sciences, 19, 1299-1315. doi:10.7150/ijbs.79260. https://pubmed.ncbi.nlm.nih.gov/36923925/