Mydgf-KO Mouse

Myeloid-derived growth factor (Mydgf), a paracrine protein secreted by bone marrow-derived monocytes and macrophages, plays crucial roles in multiple biological processes. It is involved in pathways such as c-Myc/FoxM1, MAP4K4/Akt-1/FoxO3a, and MAP4K4/NF-κB, and is important for tissue repair, anti-inflammatory responses, and maintaining cellular homeostasis [1,2,3]. Genetic mouse models like global Mydgf knockout (Mydgf-KO) have been valuable for studying its functions.

In Mydgf-KO neonatal mice, heart regeneration and injury-induced cardiomyocyte proliferation were impeded, indicating Mydgf's role in neonatal heart regeneration by activating the c-Myc/FoxM1 pathway [1]. Myeloid cell-specific Mydgf deficiency in mice exacerbated vascular inflammation, adhesion responses, endothelial injury, and atherosclerosis, while its restoration alleviated these conditions, suggesting Mydgf inhibits endothelial inflammation and protects against atherosclerosis through the MAP4K4/NF-κB signaling [3]. In pressure-overloaded Mydgf -/- mice, more severe left ventricular hypertrophy and contractile dysfunction occurred compared to wild-type mice, showing Mydgf's protective role against pressure overload-induced heart failure [4]. Tubule-specific deletion of Mydgf in mice exacerbated kidney injury in chronic kidney disease, while Mydgf overexpression attenuated kidney fibrosis by remodeling mitochondrial homeostasis [5]. Myeloid cell-specific Mydgf deficiency in mice decreased bone mass and strength, and MYDGF deficiency in mice with diabetic kidney disease caused more severe podocyte injury [6,7].

In conclusion, Mydgf plays essential roles in heart regeneration, protection against cardiovascular diseases, kidney disease, and bone metabolism. Studies using Mydgf KO mouse models have revealed its functions in these disease areas, highlighting its potential as a therapeutic target for reversing cardiac remodeling, treating atherosclerosis, heart failure, chronic kidney disease, and osteoporosis [1,3,4,5,6].

References:

1. Wang, Yuyao, Li, Yan, Feng, Jie, Liu, Lihui, Nie, Yu. 2020. Mydgf promotes Cardiomyocyte proliferation and Neonatal Heart regeneration. In Theranostics, 10, 9100-9112. doi:10.7150/thno.44281. https://pubmed.ncbi.nlm.nih.gov/32802181/

2. Xu, Jinling, Ma, Huaxing, Shi, Lingfeng, Yue, Ling, Xiang, Guangda. 2023. Inflammatory Cell-Derived MYDGF Attenuates Endothelial LDL Transcytosis to Protect Against Atherogenesis. In Arteriosclerosis, thrombosis, and vascular biology, 43, e443-e467. doi:10.1161/ATVBAHA.123.319905. https://pubmed.ncbi.nlm.nih.gov/37767706/

3. Meng, Biying, Li, Yixiang, Ding, Yan, Xiang, Lingwei, Xiang, Guangda. 2021. Myeloid-derived growth factor inhibits inflammation and alleviates endothelial injury and atherosclerosis in mice. In Science advances, 7, . doi:10.1126/sciadv.abe6903. https://pubmed.ncbi.nlm.nih.gov/34020949/

4. Korf-Klingebiel, Mortimer, Reboll, Marc R, Polten, Felix, Wang, Yong, Wollert, Kai C. 2021. Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving Sarco/Endoplasmic Reticulum Ca2+-ATPase Expression in Cardiomyocytes. In Circulation, 144, 1227-1240. doi:10.1161/CIRCULATIONAHA.120.053365. https://pubmed.ncbi.nlm.nih.gov/34372689/

5. Liu, Xiaohan, Zhang, Yang, Wang, Youzhao, Yi, Fan, Liu, Min. 2024. Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2409756. doi:10.1002/advs.202409756. https://pubmed.ncbi.nlm.nih.gov/39587987/

6. Xu, Xiaoli, Li, Yixiang, Shi, Lingfeng, Xiang, Lingwei, Xiang, Guangda. 2022. Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation. In EMBO reports, 23, e53509. doi:10.15252/embr.202153509. https://pubmed.ncbi.nlm.nih.gov/35068044/

7. He, Mingjuan, Li, Yixiang, Wang, Li, Xiang, Lingwei, Xiang, Guangda. 2020. MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease. In Diabetologia, 63, 1916-1931. doi:10.1007/s00125-020-05197-2. https://pubmed.ncbi.nlm.nih.gov/32588068/