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, playing a role in processes like bridging different ECM structures and assisting collagen secretion [4,5]. It has been associated with multiple fibrotic conditions and is involved in pathways such as TGF-β signaling [2].

In pancreatic fibrosis, COMP is up-regulated in fibrotic tissues of chronic pancreatitis (CP) patients. Knockdown of COMP in human pancreatic stellate cells (HPSCs) inhibits their proliferation and migration, while recombinant human COMP (rCOMP) promotes HPSCs activation through the CD36-ERK/AKT signaling pathway, suggesting COMP may be a potential therapeutic target for CP [1]. In atrial fibrillation, COMP knockdown inhibits the activation of the TGF-β pathway in AF cells, and COMP can improve Ang-II-induced AF via the TGF-β signaling pathway [2]. In lung transplantation, higher COMP serum levels early after transplantation are associated with the development of restrictive allograft syndrome (RAS), indicating it could be a biomarker for RAS [3]. In pseudoachondroplasia, mutations in COMP cause abnormal chondrocyte function due to protein misfolding and retention in the endoplasmic reticulum [4].

In conclusion, COMP has essential functions in maintaining ECM integrity and is involved in multiple disease-related processes. Studies, especially those using knockdown approaches, have revealed its role in fibrosis-related diseases like pancreatic fibrosis, atrial fibrillation, and RAS after lung transplantation, as well as in skeletal disorders such as pseudoachondroplasia. These findings contribute to understanding disease mechanisms and potentially developing new therapeutic strategies.

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/

5. Schulz, Jan-Niklas, Nüchel, Julian, Niehoff, Anja, Zaucke, Frank, Eckes, Beate. 2016. COMP-assisted collagen secretion--a novel intracellular function required for fibrosis. In Journal of cell science, 129, 706-16. doi:10.1242/jcs.180216. https://pubmed.ncbi.nlm.nih.gov/26746240/