POSTN(+) fibroblasts and SPP1(+) macrophages in scar formation: A review of mechanisms and therapeutic targets (Review)

Scar formation is a physiological process that occurs as a repair mechanism following tissue damage, often presenting as scar tissue at the site of injury. This process entails intricate biological responses that are intended to restore both the structure and function of the damaged tissue. Fibroblasts, the principal cells involved in scar tissue formation, are responsible for synthesizing collagen and various extracellular matrix components, all of which are vital for restoring tissue structure. During the inflammatory phase, macrophages fulfill a critical role through clearing dead cells and pathogens, and also by secreting cytokines that regulate fibroblast activity, thereby promoting the healing process. Recent studies have demonstrated that macrophages labeled with secreted phosphoprotein 1 (SPP1) and fibroblasts labeled with periostin (POSTN) are essential for scar formation, and their interaction may represent a crucial element in this process. Through performing literature searches, the aim of the present study was to further investigate the roles and mechanisms of SPP1(+) macrophages and POSTN(+) fibroblasts in scar formation, highlighting their potential synergistic crosstalk as a novel driver of fibrosis. Furthermore, the present study systematically analyzed their individual contributions, their interaction via signaling pathways and the molecular mechanisms underlying their pro‑fibrotic effects, thereby filling a critical gap in current research by focusing on specific cellular subpopulations. Furthermore, the clinical implications of targeting these specific cell subsets are discussed and this discussion provides valuable insights into the pathophysiology of these conditions, thereby establishing a theoretical basis for the development of targeted therapies for abnormal scar formation.