Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats with established renal injury

Dworkin, Lance D.; Gong, Rujun; Tolbert, Evelyn; Centracchio, Jason; Yano, Nahiro; Zanabli, Abdul R.; Esparza, Alfredo R.; Rifai, Abdalla

doi:10.1111/j.1523-1755.2004.00417.x

Cited by 66 publications

(55 citation statements)

References 23 publications

(36 reference statements)

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“…In part, this may be related to HGF's activity of suppressing TGF- (258,287). Treatment with HGF suppressed, and blockade of HGF worsened, experimental renal fibrosis (287)(288)(289). Importantly, HGF administration synergized with angiotensin-II blockade in antagonizing renal fibrosis (290).…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Section: Connective Tissue Growth Factormentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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“…The ability of HGF to inhibit tissue fibrotic lesions has been attested extensively in a wide variety of organs, including kidney (3)(4)(5)(6). Growing evidence demonstrates that administration of HGF protein or its gene prevents the progressive loss of kidney functions in chronic renal diseases with diverse causes (7)(8)(9)(10)(11). Accordingly, blockade of HGF signaling by a neutralizing antibody markedly exacerbates the progression of renal fibrosis and dysfunctions (12,13).…”

mentioning

confidence: 99%

A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal Transition

Yang¹,

Dai²,

Liu³

2005

Journal of the American Society of Nephrology

167

141

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“…Hepatocyte growth factor (HGF) has recently emerged as a potent antifibrogenic factor that prevents the onset and progression of a wide variety of CKD, including genetic ICR strainderived glomerulonephritis (7), obstructive nephropathy (8 -10), remnant kidney (11,12), chronic allograft nephropathy (13), and cyclosporin A nephropathy (14). In vitro, HGF specifically antagonizes the profibrotic actions of TGF-␤1 and blocks myofibroblast activation from interstitial fibroblasts and mesenchymal transition from tubular epithelial cells (10,15).…”

mentioning

confidence: 99%

Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice

Dai

Yang²,

Bastacky³

et al. 2004

Journal of the American Society of Nephrology

109

107

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Abstract. Diabetic nephropathy is characterized by progressive loss of renal function, persistent proteinuria, and relentless accumulation of extracellular matrix leading to glomerulosclerosis and interstitial fibrosis. This study investigated the potential effects of long-term expression of exogenous hepatocyte growth factor (HGF) on normal and diabetic kidneys. Intravenous injection of human HGF gene via naked plasmid vector resulted in abundant HGF protein specifically localized in renal glomeruli, despite an extremely low level of transgene mRNA in the kidney. In uninephrectomized mice made diabetic with streptozotocin, delivery of exogenous HGF gene ameliorated the progression of diabetic nephropathy. HGF attenuated urine albumin and total protein excretion in diabetic mice. Exogenous HGF also mitigated glomerular mesangial expansion, reduced fibronectin and type I collagen deposition, and prevented interstitial myofibroblast activation. In addition, HGF prevented kidney cells from apoptotic death in the glomeruli and tubulointerstitium. Moreover, expression of HGF inhibited renal expression of TGF-␤1 and reduced urine level of TGF-␤1 protein. Therefore, despite the effects of HGF on diabetic nephropathy being controversial, these observations suggest that supplementation of HGF is beneficial in ameliorating diabetic renal insufficiency in mice.Diabetic nephropathy (DN) is the leading cause of chronic kidney diseases (CKD) that ultimately progress to end-stage renal failure (1,2). The number of patients who are afflicted with DN is steadily increasing worldwide, mainly as a result of a growing population of type 2 diabetes. The pathogenesis of DN is characterized by progressive loss of renal function, persistent proteinuria, and accumulation of extracellular matrix (ECM) that leads to glomerulosclerosis and tubulointerstitial fibrosis (3). Current therapy only slows but does not inhibit the progression of diabetic renal insufficiency in clinical settings (4 -6). Therefore, new therapeutic approaches are needed to halt the progressive loss of renal function in patients who have this devastating illness.Hepatocyte growth factor (HGF) has recently emerged as a potent antifibrogenic factor that prevents the onset and progression of a wide variety of CKD, including genetic ICR strainderived glomerulonephritis (7), obstructive nephropathy (8 -10), remnant kidney (11,12), chronic allograft nephropathy (13), and cyclosporin A nephropathy (14). In vitro, HGF specifically antagonizes the profibrotic actions of TGF-␤1 and blocks myofibroblast activation from interstitial fibroblasts and mesenchymal transition from tubular epithelial cells (10,15). In vivo, HGF inhibits renal TGF-␤1 expression and mitigates fibrotic lesions after various chronic injuries (10,12,16,17). Recent studies indicate that the antifibrotic actions of HGF are primarily mediated by specifically interrupting TGF-␤1/Smad signal transduction (15,18,19). In view of a causative role of hyperactive TGF-␤1 signaling in the initiation and development of ...

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Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats with established renal injury

Abstract: These findings suggest that HGF can retard progression of chronic renal disease even after injury is already established, primarily by promoting matrix degradation.

Cited by 66 publications

References 23 publications

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Renal Allograft Fibrosis: Biology and Therapeutic Targets

A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal Transition

Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice

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