Comp-KO Mouse

COMP, also known as cartilage oligomeric matrix protein, is an extracellular matrix (ECM) glycoprotein. It is critical for collagen assembly and ECM stability, and has been associated with multiple fibrotic conditions. COMP regulates the TGF-β signaling pathway and may interact with membrane protein receptor CD36 to activate certain signaling pathways [1,2].

In a mouse model of chronic pancreatitis (CP), COMP was up-regulated in fibrotic tissues. Knockdown of COMP in human pancreatic stellate cells (HPSCs) inhibited their proliferation and migration, while recombinant human COMP (rCOMP) promoted HPSCs activation, potentially by promoting the phosphorylation of ERK and AKT through CD36 [1]. In Ang-II-induced atrial fibrillation in mice, silencing COMP inhibited the activation of the TGF-β pathway in atrial fibrillation cells [2]. In lung transplantation patients, higher mean COMP levels early after transplantation were associated with the development of restrictive allograft syndrome (RAS) [3]. In pseudoachondroplasia, mutations in COMP interfere with calcium-binding and protein conformation, leading to impaired chondrocyte function [4].

In conclusion, COMP plays essential roles in fibrosis-related processes, atrial fibrillation, and post-lung-transplantation complications. Studies using gene-knockdown or-knockout models have revealed its function in these disease conditions, highlighting its potential as a therapeutic target or biomarker.

References:

1. Wang, Yi, Li, Hai-Tao, Liu, Gang, Wang, Wen, Zeng, Xiang-Peng. 2024. COMP promotes pancreatic fibrosis by activating pancreatic stellate cells through CD36-ERK/AKT signaling pathways. In Cellular signalling, 118, 111135. doi:10.1016/j.cellsig.2024.111135. https://pubmed.ncbi.nlm.nih.gov/38479555/

2. Cai, XiaoBi, Li, Mingliang, Zhong, Ying, Yang, Wenkun, Liang, Zhu. 2023. COMP Improves Ang-II-Induced Atrial Fibrillation via TGF-β Signaling Pathway. In Cardiovascular toxicology, 23, 305-316. doi:10.1007/s12012-023-09799-1. https://pubmed.ncbi.nlm.nih.gov/37584842/

3. Novo, Mirza, Westin, Johan, Andersson, Lars-Magnus, Nordén, Rickard, Magnusson, Jasper M. 2021. COMP: A Potential Early Biomarker of RAS After Lung Transplantation. In Transplantation direct, 7, e730. doi:10.1097/TXD.0000000000001189. https://pubmed.ncbi.nlm.nih.gov/34291152/

4. Posey, Karen L, Hayes, Elizabeth, Haynes, Richard, Hecht, Jacqueline T. . Role of TSP-5/COMP in pseudoachondroplasia. In The international journal of biochemistry & cell biology, 36, 1005-12. doi:. https://pubmed.ncbi.nlm.nih.gov/15094116/