Work

Macrophage Plasticity and Regulatory Networks During the Transition from Inflammation to Fibrosis in the Kidney

Year: 2025

Type: article

Abstract: Kidney fibrosis represents the final common pathway of nearly all progressive renal diseases, linking acute kidney injury (AKI) and chronic kidney disease (CKD) through a maladaptive repair process. Regardless of etiology, persistent inflammation and excessive extracellular matrix (ECM) deposition drive irreversible structural distortion and functional decline in the kidney. Among cellular mediators, macrophages occupy a central role across the continuum from acute injury to fibrosis, orchestrating both tissue injury and repair through dynamic transitions between pro-inflammatory (M1) and pro-fibrotic (M2) states in response to local cues. Here, we synthesize macrophage-driven mechanisms of renal fibrosis, emphasizing recruitment, infiltration, and local proliferation mediated by chemokine-receptor networks and mechanosensitive ion channels. In addition, in this review paper, we provide an overview on the dual roles of macrophages in acute inflammation and chronic remodeling through key cytokine signaling pathways (TLR4/NF-κB, IL-4/STAT6, TGF-β/Smad, IL-10/STAT3), highlighting how metabolic reprogramming, mechanochemical feedback via Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling, and epigenetic modulators collectively stabilize the fibrotic macrophage phenotype. Also, emerging insights into mitochondrial dysfunction, succinate-succinate receptor 1 (SUCNR1) signaling, and autophagy dysregulation reveal the metabolic basis of macrophage persistence in fibrotic kidneys. Understanding these multilayered regulatory circuits offers a framework for therapeutic strategies that selectively target macrophage-dependent fibrogenesis to halt the transition from acute injury to chronic renal failure.

Source: Life

DOI: 10.3390/life16010052

Authors: Yehun Moon, Jintaek Hong, Jinwoo Chung, Jea-Hyun Baek

Institution: Handong Global University

Language: English

Topic: Chronic Kidney Disease and Diabetes

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137