CREG1, the cellular repressor of E1A-stimulated genes 1, is a glycoprotein involved in multiple biological processes. It plays a role in tissue homeostasis, cell differentiation, and energy metabolism. CREG1 is associated with pathways like autophagy, mitophagy, and those related to glucose and lipid metabolism [1,2,5]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in uncovering its functions.

In KO mouse models, CREG1 deficiency has diverse impacts. In diabetic cardiomyopathy, it exacerbates cardiac dysfunction, hypertrophy, and fibrosis, along with autophagy dysfunction, indicating CREG1's protective role via promoting autophagy [1]. In skeletal muscle, CREG1 -deficient mice show reduced exercise endurance, abnormal mitochondrial quality, and accelerated mitophagy induction [2]. In doxorubicin -induced cardiotoxicity, CREG1 deficiency aggravates the toxicity and ferroptosis in cardiomyocytes [3]. Also, CREG1 -deficient mice have impaired myoblast differentiation and skeletal muscle regeneration, as well as thrombocytopenia due to inefficient thrombopoiesis [4,6].

In conclusion, CREG1 is essential for various biological functions including cardiac, skeletal muscle, and hematopoietic functions. The KO and CKO mouse models have significantly contributed to understanding its role in diseases like diabetic cardiomyopathy, doxorubicin -induced cardiotoxicity, and thrombocytopenia, providing potential therapeutic targets for these conditions.

References:

1. Liu, Dan, Xing, Ruinan, Zhang, Quanyu, Yan, Chenghui, Han, Yaling. 2023. The CREG1-FBXO27-LAMP2 axis alleviates diabetic cardiomyopathy by promoting autophagy in cardiomyocytes. In Experimental & molecular medicine, 55, 2025-2038. doi:10.1038/s12276-023-01081-2. https://pubmed.ncbi.nlm.nih.gov/37658156/

2. Song, HaiXu, Tian, Xiaoxiang, Liu, Dan, Yan, Chenghui, Han, Yaling. 2021. CREG1 improves the capacity of the skeletal muscle response to exercise endurance via modulation of mitophagy. In Autophagy, 17, 4102-4118. doi:10.1080/15548627.2021.1904488. https://pubmed.ncbi.nlm.nih.gov/33726618/

3. Liu, Dan, Cheng, Xiaoli, Wu, Hanlin, Yan, Chenghui, Han, Yaling. 2024. CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes. In Redox biology, 75, 103293. doi:10.1016/j.redox.2024.103293. https://pubmed.ncbi.nlm.nih.gov/39094399/

4. Song, Haixu, Tian, Xiaoxiang, He, Lianqi, Yan, Chenghui, Han, Yaling. 2024. CREG1 deficiency impaired myoblast differentiation and skeletal muscle regeneration. In Journal of cachexia, sarcopenia and muscle, 15, 587-602. doi:10.1002/jcsm.13427. https://pubmed.ncbi.nlm.nih.gov/38272853/

5. Goto, Ayumi, Endo, Yuki, Yamashita, Hitoshi. 2022. CREG1 stimulates AMPK phosphorylation and glucose uptake in skeletal muscle cells. In Biochemical and biophysical research communications, 641, 162-167. doi:10.1016/j.bbrc.2022.12.028. https://pubmed.ncbi.nlm.nih.gov/36528955/

6. Song, HaiXu, Li, Jiayin, Peng, Chengfei, Yan, Chenghui, Han, Yaling. 2023. The role of CREG1 in megakaryocyte maturation and thrombocytopoiesis. In International journal of biological sciences, 19, 3614-3627. doi:10.7150/ijbs.78660. https://pubmed.ncbi.nlm.nih.gov/37496998/