The fibrogenic niche in kidney fibrosis: components and mechanisms

作者：Li, Li; Fu, Haiyan; Liu, Youhua^*

来源：NATURE REVIEWS NEPHROLOGY, 2022, 18(9): 545-557.

DOI：10.1038/s41581-022-00590-z

• TO-MESENCHYMAL TRANSITION
• TISSUE GROWTH-FACTOR
• EXTRACELLULAR-MATRIX
• TENASCIN-C
• RENAL FIBROSIS
• RECEPTOR 4
• TGF-BETA
• INTERSTITIAL FIBROBLASTS
• MOLECULAR-MECHANISMS
• PODOCYTE INJURY

Kidney fibrosis, characterized by excessive deposition of extracellular matrix (ECM) that leads to tissue scarring, is the final common outcome of a wide variety of chronic kidney diseases. Rather than being distributed uniformly across the kidney parenchyma, renal fibrotic lesions initiate at certain focal sites in which the fibrogenic niche is formed in a spatially confined fashion. This niche provides a unique tissue microenvironment that is orchestrated by a specialized ECM network consisting of de novo-induced matricellular proteins. Other structural elements of the fibrogenic niche include kidney resident and infiltrated inflammatory cells, extracellular vesicles, soluble factors and metabolites. ECM proteins in the fibrogenic niche recruit soluble factors including WNTs and transforming growth factor-beta from the extracellular milieu, creating a distinctive profibrotic microenvironment. Studies using decellularized ECM scaffolds from fibrotic kidneys show that the fibrogenic niche autonomously promotes fibroblast proliferation, tubular injury, macrophage activation and endothelial cell depletion, pathological features that recapitulate key events in the pathogenesis of chronic kidney disease. The concept of the fibrogenic niche represents a paradigm shift in understanding of the mechanism of kidney fibrosis that could lead to the development of non-invasive biomarkers and novel therapies not only for chronic kidney disease, but also for fibrotic diseases of other organs. @@@ The fibrogenic niche is a unique tissue microenvironment that promotes fibroblast activation in organ fibrosis. This Review discusses the composition, function and mechanisms of action of the fibrogenic niche in kidney fibrosis, as well as the potential implications of the fibrogenic niche hypothesis for the future diagnosis and treatment of kidney diseases.

• 单位
  南方医科大学