SMOC2, also known as secreted modular calcium-binding protein 2, is a non-structural component of the extracellular matrix. It has been implicated in various biological processes and disease conditions. SMOC2 may be involved in pathways such as TGF-β1/Smad3, integrin β3-FAK-paxillin, and BMP/TGF-β1, playing important roles in tissue remodeling, cell behavior regulation, and potentially in the development of some diseases [1,2,3,6]. Genetic models like knockout (KO) mice are valuable tools for studying its functions.

In fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA), SMOC2 knockdown regulated cytoskeleton remodeling and decreased FLSs migration and invasion, suggesting its role in synovial aggression and joint destruction in RA [1]. In renal cell carcinoma, SMOC2 promoted an epithelial-mesenchymal transition and a pro-metastatic phenotype, and its knockdown inhibited related processes [2]. In heart failure and myocardial fibrosis models, SMOC2 knockdown improved cardiac function and alleviated fibrosis by modulating relevant signaling pathways [3,4]. In the dorsal root ganglion (DRG), Smoc2 KO mice showed increased neuronal clusters and decreased mechanical threshold, indicating its role in suppressing mechanical nociception [5]. In abdominal aortic aneurysm, overexpression of SMOC2 promoted vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix degradation, while its silence had the opposite effect [6].

In conclusion, SMOC2 is involved in a wide range of biological functions including cell migration, proliferation, and extracellular matrix-related processes. Studies using KO mouse models have revealed its significance in diseases such as RA, renal cell carcinoma, heart-related diseases, nociception regulation, and abdominal aortic aneurysm, providing potential therapeutic targets for these conditions.

References:

1. Liu, Di, Li, Ruiru, Xu, Siqi, Xiao, Youjun, Xu, Hanshi. 2022. SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C. In Cell death & disease, 13, 1035. doi:10.1038/s41419-022-05479-0. https://pubmed.ncbi.nlm.nih.gov/36513634/

2. Feng, Daniel, Gao, Peng, Henley, Nathalie, Pichette, Vincent, Gerarduzzi, Casimiro. 2022. SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin. In Cell death & disease, 13, 639. doi:10.1038/s41419-022-05059-2. https://pubmed.ncbi.nlm.nih.gov/35869056/

3. Ren, Yu, Wu, Yun, He, Wenshuai, Tian, Yingjie, Zhao, Xingsheng. 2023. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy. In Open medicine (Warsaw, Poland), 18, 20230752. doi:10.1515/med-2023-0752. https://pubmed.ncbi.nlm.nih.gov/37465345/

4. Rui, Huang, Zhao, Fang, Yuhua, Lei, Hong, Jiang. 2023. Suppression of SMOC2 alleviates myocardial fibrosis via the ILK/p38 pathway. In Frontiers in cardiovascular medicine, 9, 951704. doi:10.3389/fcvm.2022.951704. https://pubmed.ncbi.nlm.nih.gov/36935650/

5. Zhang, Shuo, Cai, Bing, Li, Zhen, Li, Changlin, Zhang, Xu. 2022. Fibroblastic SMOC2 Suppresses Mechanical Nociception by Inhibiting Coupled Activation of Primary Sensory Neurons. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 42, 4069-4086. doi:10.1523/JNEUROSCI.2132-21.2022. https://pubmed.ncbi.nlm.nih.gov/35437277/

6. Wang, Xiaowei, Wang, Meng, Zhou, Zhongxiao, Zhang, Qingsong, Zhou, Haimeng. 2023. SMOC2 promoted vascular smooth muscle cell proliferation, migration, and extracellular matrix degradation by activating BMP/TGF-β1 signaling pathway. In Journal of clinical biochemistry and nutrition, 73, 116-123. doi:10.3164/jcbn.22-100. https://pubmed.ncbi.nlm.nih.gov/37700850/