Fibrosis Mechanisms in Chronic Kidney Disease
Summary
The hallmark of chronic kidney disease (CKD) is progressive scarring or fibrosis, driven by an imbalance between injury and repair within the renal parenchyma. Upon persistent insult—metabolic, haemodynamic or toxic—there is activation of resident fibroblasts and recruitment of immune cells. This leads to excessive deposition of extracellular matrix (ECM) proteins, distortion of nephron architecture and decline of glomerular filtration. Transforming growth factor β (TGF-β), a master profibrotic cytokine, orchestrates myofibroblast differentiation, epithelial-to-mesenchymal transition (EMT) and ECM synthesis. Emerging evidence highlights epigenetic regulation, cellular plasticity unveiled by single-cell analysis and crosstalk among tubular epithelial cells, pericytes and macrophages as central to progression. Therapeutic strategies now target signalling cascades, metabolic reprogramming and matrix remodelling to halt or reverse scarring and preserve renal function.
Research from Nature Portfolio
Recent studies have utilised single-cell transcriptomic profiling to resolve distinct fibroblast and inflammatory cell subsets in fibrotic kidneys, identifying a pathogenic myofibroblast cohort characterised by high expression of collagen and chemokines. Parallel work has elucidated an epigenetic switch in tubular epithelial cells, whereby altered DNA methylation patterns sustain TGF-β-driven mesenchymal reprogramming. A third investigation demonstrated a novel small-molecule inhibitor of the TGF-β receptor that effectively attenuates myofibroblast activation and extracellular matrix accumulation in preclinical models, setting the stage for early-phase therapeutic trials.
Fibrosis Mechanisms in Chronic Kidney Disease publication trend
The graph below shows the total number of articles in fibrosis mechanisms in chronic kidney disease across all publications each year (not limited to Nature Index journals).
Technical terms
Extracellular matrix (ECM): A network of collagens and glycoproteins that provides structural support and signalling cues in tissues.
Transforming growth factor β (TGF-β): A cytokine that drives myofibroblast activation, EMT and ECM synthesis during fibrosis.
Epithelial-to-mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal features and contribute to fibrotic cell populations.
Fibroblast: A resident stromal cell that differentiates into a myofibroblast, secreting ECM components and contractile proteins.
Single-cell transcriptomics: A technology to profile gene expression at the level of individual cells, revealing cellular heterogeneity.
Epigenetic modification: Heritable changes in gene expression, such as DNA methylation, that do not involve alterations in DNA sequence.
Cdc42: A small GTPase involved in cytoskeletal dynamics and signalling pathways implicated in fibroblast activation.
References
- A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42‐mediated GSK‐3β/β‐catenin Signaling. Advanced Science (2024).
- Anlotinib Alleviates Renal Fibrosis via Inhibition of the ERK and AKT Signaling Pathways. Oxidative Medicine and Cellular Longevity (2023).
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