Paracrine

Paracrine signaling is a mode of cell-to-cell communication in which a cell secretes signaling molecules that act on nearby target cells within the same tissue or microenvironment. The secreted factors—such as growth factors, cytokines, chemokines, prostaglandins, nitric oxide, and other small molecules—diffuse through the extracellular space to bind to receptors on neighboring cells. Because the signals act over short distances and are rapidly degraded, paracrine effects are typically tightly localized.

Paracrine signaling is distinct from autocrine signaling, where the secreting cell also responds to its own signal, and from endocrine signaling, where signals enter the bloodstream to reach distant targets. In paracrine communication, the distance is usually limited to adjacent cells within a tissue, allowing fine spatial and temporal control of tissue development, homeostasis, and responses to injury.

Examples include epidermal growth factor produced by keratinocytes acting on nearby epithelial cells, platelet-derived growth factor, transforming growth factor-beta, interleukins, vascular endothelial growth factor in angiogenesis, and nitric oxide synthesized by endothelial cells to relax adjacent smooth muscle. In the nervous system, several neuroactive substances can act in a paracrine fashion to modulate local circuits.

Paracrine signaling can be regulated by factors such as receptor density, ligand stability, degradation by extracellular proteases, and diffusion barriers created by the extracellular matrix. It interacts with autocrine and endocrine pathways to coordinate complex physiological processes.

Dysregulation of paracrine signaling has been implicated in diseases including cancer, chronic inflammation, and fibrosis, where local signaling loops promote aberrant cell growth, survival, or tissue remodeling.