Renal fibrosis

Abstract

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

Keywords: Fibrosis; Glomerulosclerosis; Kidney disease.

Fig. 1

Pathologic findings of contralateral (A) and ipsilateral (B) kidney in C57BL/6 mice with UUO (day 7). Contralateral kidney without UUO shows intact glomerular and tubulointerstitial structure (A), whereas ipsilateral kidney with UUO shows tubulointerstitial fibrosis, tubular atrophy, and glomerulosclerosis (B). Kidney sections (2-µm thickness) were stained with Masson trichrome staining. Abbreviation: UUO, unilateral ureteral obstruction.

Fig. 2

Pathogenetic mechanism underlying renal fibrosis. Initial renal damage can induce both cellular and molecular activation. Cellular activation may subsequently provoke the activation of signal molecules. Both cellular activations such as EMT, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and molecular activations such as TGF-β, AngII, CTGF, PDGF, ET-1, TNF-α, and IL-1 result in the excessive accumulation of ECM. Antifibrotic cytokines such as HGF, BMP-7, IFN-γ, and IGF-1 or several proteases such as MMP, plasminogen activator, and lysosomal cathepsins may attenuate renal fibrosis. Modified from Eddy SS. Abbreviations: EMT: epithelial-to-mesenchymal transition, TGF-β: transforming growth factor beta, AngII: angiotensin II, CTGF: connective tissue growth factor, PDGF: platelet-derived growth factor, ET-1: endothelin-1, TNF-α: tumor necrosis factor alpha, IL-1: interleukin 1, ECM: extracellular matrix, HGF: hepatocyte growth factor, BMP-7: bone morphogenetic protein 7, IFN-γ: interferon gamma, IGF-1: insulin-like growth factor 1, and MMP: matrix metalloproteinases.