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Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease
S Mizuno1, T Kurosawa, K Matsumoto
1The Institute of Experimental Animal Sciences, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita 565-0871, Japan.
Insights
Hepatocyte growth factor (HGF) can prevent chronic renal disease (CRD) progression by promoting tubular repair and inhibiting kidney fibrosis. This study suggests HGF therapy as a novel treatment option for CRD.
Area of Science:
- Nephrology
- Regenerative Medicine
- Molecular Biology
Background:
- Chronic renal disease (CRD) is a growing global health concern, often leading to end-stage kidney failure.
- Current treatments for CRD are limited, with renal transplantation being the primary curative option.
- Glomerulosclerosis and tubulointerstitial fibrosis are key pathological features of advanced CRD.
Purpose of the Study:
- To investigate the potential of hepatocyte growth factor (HGF) in preventing the progression of chronic renal disease.
- To evaluate the effects of HGF on renal dysfunction, fibrosis, and cellular repair in a mouse model of CRD.
Main Methods:
- Utilized a spontaneous mouse model (ICGN strain) that naturally develops CRD.
- Administered recombinant HGF to mice during a critical 4-week period of disease progression.
- Assessed changes in tubular epithelial cell DNA synthesis, growth factor expression (TGF-β, PDGF), myofibroblast formation, and overall renal function.
Main Results:
- HGF significantly increased tubular epithelial cell DNA synthesis, indicating enhanced tissue repair.
- HGF suppressed key fibrotic markers, including transforming growth factor-beta and platelet-derived growth factor, and reduced myofibroblast accumulation.
- HGF administration almost completely inhibited tubulointerstitial fibrosis and attenuated glomerulosclerosis, thereby preventing the decline in renal function.
Conclusions:
- Hepatocyte growth factor demonstrates significant preventive effects against the progression of chronic renal disease in a mouse model.
- HGF promotes tubular regeneration and inhibits renal fibrosis, offering a potential therapeutic strategy.
- HGF supplementation may represent a novel approach for the prevention and treatment of chronic renal disease.
Abstract:
Chronic renal disease (CRD) is generally thought to be incurable, except through renal transplantation, and the number of patients with CRD is on the increase. Glomerulosclerosis and tubulointerstitial fibrosis represent the morphological equivalent of end-stage CRD. In this study, we demonstrated the preventive effect of hepatocyte growth factor (HGF) on the progression of renal dysfunction and fibrosis, using a spontaneous mouse model for CRD (ICGN strain). The mice progressively developed glomerular sclerotic injury, tubular atrophy, and renal dysfunction until they were 17 wk of age. When recombinant HGF was injected into these mice during a 4-wk-period (from weeks 14-17 after birth), DNA synthesis of tubular epithelial cells was found to be 4.4-fold higher than in mice without HGF injection, thereby suggesting tubular parenchymal expansion promoted by HGF. Notably, HGF suppressed the expression of transforming growth factor-beta and of platelet-derived growth factor as well as myofibroblast formation in the affected kidney. Consequently, the onset of tubulointerstitial fibrosis was almost completely inhibited by HGF, while HGF attenuated the progression of glomerulosclerosis, both leading to preventing manifestation of renal dysfunction. From our results, supplement therapy with HGF may be taken into consideration as a novel option for prevention and treatment of CRD.
