Macrophage-Fibroblast Crosstalk in Kidney Injury: A Narrative Review

Renal fibrosis is a multifaceted pathological process driven by cellular interactions, with fibroblasts and macrophages serving as central regulators. Fibroblasts activate into matrix-producing myofibroblasts, directly contributing to fibrogenesis and disease progression. Macrophages, characterized by pronounced heterogeneity, dynamically modulate the balance between tissue injury and repair, thereby critically influencing disease outcomes. The crosstalk between these two cell types operates through diverse signaling pathways, extracellular vesicle-mediated communication, and metabolic reprogramming, forming an intricate regulatory network that exerts stage-specific effects during renal injury. Recent insights into fibroblast activation, macrophage polarization, and their intercellular interplay have provided potential therapeutic avenues for delaying kidney fibrosis, offering renewed promise for clinical translation.