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 promoting tissue repair and regulating cell proliferation, inflammation, and mitochondrial homeostasis. The c-Myc/FoxM1, MAP4K4/Akt-1/FoxO3a, and MAP4K4/NF-κB pathways are among those associated with its functions. Genetic mouse models, such as Mydgf knockout (Mydgf-KO), have been essential in studying Mydgf's functions [1,2,3].

In Mydgf-KO neonatal mice, heart regeneration and injury-induced cardiomyocyte proliferation were impeded, indicating Mydgf's role in neonatal heart regeneration through activation of the c-Myc/FoxM1 pathway [1]. Myeloid cell-specific Mydgf-KO in mice exacerbated vascular inflammation, adhesion responses, endothelial injury, and atherosclerosis, suggesting Mydgf inhibits these processes via the MAP4K4/NF-κB signaling [3]. Mydgf -/- mice also developed more severe left ventricular hypertrophy and contractile dysfunction during pressure overload compared to wild-type mice, showing its protective role against pressure-overload-induced heart failure [4]. In the context of kidney diseases, tubule-specific deletion of Mydgf exacerbated kidney injury in CKD mice, highlighting its importance in maintaining kidney function [5].

In conclusion, Mydgf is essential for tissue repair, cell proliferation, and anti-inflammatory responses in various organs. The use of Mydgf-KO mouse models has significantly contributed to understanding its role in diseases such as heart failure, atherosclerosis, and kidney diseases, providing potential therapeutic targets for these conditions.