Cellular and molecular mechanisms of renal fibrosis

By Youhua Liu. Nature Reviews Nephrology, 2011

1,376 citations recorded by the source corpus.

Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final outcome of almost all progressive chronic kidney diseases. Renal fibrosis is also a reliable predictor of prognosis and a major determinant of renal insufficiency. Irrespective of the initial causes, renal fibrogenesis is a dynamic and converging process that consists of four overlapping phases: priming, activation, execution and progression. Nonresolving inflammation after a sustained injury sets up the fibrogenic stage (priming) and triggers the activation and expansion of matrix-producing cells from multiple sources through diverse mechanisms, including activation of interstitial fibroblasts and pericytes, phenotypic conversion of tubular epithelial and endothelial cells and recruitment of circulating fibrocytes. Upon activation, matrix-producing cells assemble a multicomponent, integrin-associated protein complex that integrates input from various fibrogenic signals and orchestrates the production of matrix components and their extracellular assembly. Multiple cellular and molecular events, such as tubular atrophy, microvascular rarefaction and tissue hypoxia, promote scar formation and ensure a vicious progression to end-stage kidney failure. This Review outlines our current understanding of the cellular and molecular mechanisms of renal fibrosis, which could offer novel insights into the development of new therapeutic strategies.

Subfields: Immunology, Nephrology

View Paper: https://www.semanticscholar.org/paper/df8edc3382c21b1b58986e28a8d15ee1955b40f8

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. J. López-Novoa
2. B. Hinz
3. Nur Samsu

In Nephrology

1. J. López-Novoa
2. B. Hinz
3. Nur Samsu

Citations in the corpus

• Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. (2012, background): “The myofibroblast is a major player in the onset and evolution of renal fibrosis and has been implicated in pathogenesis.(107)”
• Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease (2015, methodology): “Mice were treated with (1) vehicle (corn oil, −TAM); (2) tamoxifen for 8 weeks (+TAM); (3) tamoxifen for 8 weeks followed by vehicle treatment for another 8 weeks (+TAM −TAM).”
• Protective Actions of H2S in Acute Myocardial Infarction and Heart Failure (2017, neutral): “Myofibroblast activation and proliferation are considered to be two key events of the fibrotic process (93).”
• Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment (2021, background): “Proinflammatory and fibrogenic cytokines that are synthesized and secreted by these cells in the local microenvironment can directly damage the renal architecture and then trigger the epithelial-to-mesenchymal transition (EMT) process [56], which in turn results in ECM accumulation.”