Abstract
BACKGROUND: Myocyte enhancer factor 2 (MEF2), belonging to the Minichromosome Maintenance 1, Agamous, Deficiens and Serum Response Factor (MADS) box family with four members (MEF2A-D), plays a pivotal role in the proliferation and differentiation of various cells, including endothelial cells (ECs) and fibroblasts, as well as in physiological processes such as angiogenesis. Recent research highlights the crucial importance of MEF2 in the formation of hypertrophic scar, indicating its potential significance in scar formation and angiogenesis. However, the underlying mechanisms are still largely unexplored and warrant further investigation. AIMS: This article aims to provide a detailed summary of the connections between MEF2 and both angiogenesis and scar formation, with a focus on elucidating the possible mechanisms by which MEF2 participates in angiogenesis and scar formation. METHODS: Search on the Pubmed using the keywords MEF2, Scar, and Angiogenesis. The retrieval period spanned from January to August 2025. Summarize the viewpoints of the articles and refine the mechanisms and interconnections among MEF2, Scar, and Angiogenesis. RESULTS: Imbalanced regulation of angiogenesis leads to abnormal scar formation. Although the role of MEF2 is not fully understood, it has been hypothesized as follows: MEF2 indirectly influences scar formation by regulating angiogenesis and vascular inflammatory responses, via the MAPK (mitogen-activated protein kinase) signaling pathway and its interplay with vascular endothelial growth factor (VEGF). On the other hand, MEF2 leads to abnormal deposition of extracellular matrix (ECM) and excessive activation of fibroblasts through its involvement in the transforming growth factor-β (TGF-β)/mothers against decapentaplegic (Smad) signaling pathway, ultimately leading to fibrosis and scar formation during the wound healing process. CONCLUSIONS: MEF2 is intimately associated with angiogenesis and scar formation. However, the mechanisms through which MEF2 is involved in these processes remain incompletely understood, necessitating further in-depth research at the genetic and molecular levels. An increasing number of studies suggest that MEF2 holds significant potential in anti-angiogenesis and scar treatment therapies, potentially emerging as a novel target for the treatment of pathological scars in the future.