Canonical and emerging regulatory mechanisms of tissue remodeling: shared principles across organs and therapeutic opportunities.

Tissue remodeling refers to the structural and functional alterations an organ undergoes in response to changing environmental conditions. This process is precisely regulated by complex signaling networks. While these networks are essential for physiological repair, their dysregulation can lead to pathological conditions. Traditionally, this process is driven by a core set of molecular pathways, including the TGF-β superfamily, growth factors, and the MMPs/TIMPs system. These pathways primarily influence extracellular matrix turnover and fibroblast activation. The resulting inflammatory microenvironment is further modulated by changes in the Th1/Th2 balance and macrophage polarization. Recent studies, however, have highlighted the critical role of emerging regulatory networks. Mechanical signals are now understood to be transduced through the integrin-YAP/TAZ axis. Additionally, metabolic reprogramming, mediated by the glycolysis-HIF-mTOR axis, supplies the necessary energy for cell activation. Non-coding RNAs further refine these processes through multi-level regulation. This review synthesizes both canonical and emerging mechanisms. Our aim is to uncover the shared principles underlying pathological remodeling in different organs, providing a theoretical foundation for the development of precision intervention strategies across diseases.