Sfrp2, short for Secreted Frizzled-Related Protein 2, is a vital molecule in the Wnt signaling pathway. It can act as an antagonist of the canonical Wnt signaling pathway, and is involved in regulating multiple biological processes such as organ development and disease processes [3].

In a conditional Sfrp2 knockout in cancer-associated fibroblasts (CAFs), it was found to boost the abscopal effect of radioimmunotherapy by rewiring the vascular-immune microenvironment to promote CD8+ T cell recruitment to unirradiated tumors. This indicates that SfrP2-high CAFs serve as critical stromal regulators that can hijack the abscopal effect [1]. In the context of diabetic cardiomyopathy, overexpression of Sfrp2 in a rat model reversed apoptosis and promoted mitochondrial function, while silencing endogenous SfrP2 further promoted glucolipotoxicity-induced mitochondrial dysfunction and apoptosis in cardiomyocytes. SfrP2 exerted cardioprotective effects through the AMPK-PGC1-α-dependent pathway [2].

In conclusion, Sfrp2 plays crucial roles in multiple biological processes. Its conditional knockout in CAFs reveals its significance in regulating the abscopal effect of radioimmunotherapy. In diabetic cardiomyopathy, studies on Sfrp2, including gain-and loss-of-function experiments, show its potential as a therapeutic biomarker by modulating mitochondrial function. These findings from model-based research contribute to understanding the underlying mechanisms of related diseases and offer potential therapeutic targets.

References:

1. Zhang, Yan-Pei, Guo, Ze-Qin, Cai, Xiao-Ting, Wu, De-Hua, Dong, Zhong-Yi. 2025. PAI-1-driven SFRP2high cancer-associated fibroblasts hijack the abscopal effect of radioimmunotherapy. In Cancer cell, , . doi:10.1016/j.ccell.2025.02.024. https://pubmed.ncbi.nlm.nih.gov/40086438/

2. Ma, Tianyi, Huang, Xiaohui, Zheng, Haoxiao, Hu, Yunzhao, Huang, Yuli. 2021. SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy. In Oxidative medicine and cellular longevity, 2021, 9265016. doi:10.1155/2021/9265016. https://pubmed.ncbi.nlm.nih.gov/34790288/

3. Wu, Yu, Liu, Xinyue, Zheng, Haoxiao, Huang, Xiaohui, Huang, Yuli. 2020. Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease. In International journal of biological sciences, 16, 730-738. doi:10.7150/ijbs.40923. https://pubmed.ncbi.nlm.nih.gov/32071544/