Igfbp3, or Insulin-like growth factor binding protein 3, is a multifunctional protein. It binds to IGF-1, regulating growth, survival, and aging, and is involved in multiple pathways like the IGF-1 signaling pathway. It plays significant roles in various biological processes including cell growth, apoptosis, and tissue remodeling [2,3].

In cardiac fibrosis, IGFBP3 expression significantly increases in TGF-β1-stimulated human primary cardiac fibroblasts. Knockdown of IGFBP3 inhibits the migration and proliferation ability of these cells, suggesting its role in promoting cardiac fibroblast activation and fibrosis. METTL3 may regulate IGFBP3's expression and cardiac fibroblast activation via RNA epigenetic modifications [1]. In murine cells, IGFBP3 gene knockout (KO) by the CRISPR/Cas9 system enhanced the level of SA-β-gal staining and short telomere length, and increased the expression levels of senescence-related proteins, indicating its key role in the aging mechanism [3]. In human endometrial mesenchymal stem cells, IGFBP3-knockout cells lost stemness and underwent chondrogenic differentiation [2].

In conclusion, Igfbp3 is crucial for various biological functions such as cell growth, apoptosis, and tissue-specific differentiation. Studies using Igfbp3 KO models have provided insights into its roles in diseases like cardiac fibrosis and aging-related processes, highlighting its potential as a therapeutic target in these areas.