Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli

Esposito, Ciro; Parrilla, Bina; Mauri, Andreana De; Cornacchia, Flavia; Fasoli, Gianluca; Foschi, Annalisa; Mazzullo, Tiziana; Plati, Annarita; R, Scudellaro; Canton, Antonio Dal

doi:10.1111/j.1523-1755.2005.00319.x

Cited by 25 publications

(16 citation statements)

References 20 publications

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“…Previous studies indicated that TGF-β1 and HGF are counteracting in their biological activities (Mizuno et al, 2001). TGF-β1 strongly stimulates the synthesis of ECM proteins and inhibits the degradation of ECM (Esposito et al, 2005;. In contrast, HGF accelerates the degradation of ECM by modulating proteinases involved in the breakdown of ECM proteins.…”

Section: Discussionmentioning

confidence: 99%

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Zuo

Xie

Qiu

et al. 2009

J. Zhejiang Univ. Sci. B

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Abstract:Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg·d)) UUO group, and losartan-treated (20 mg/(kg·d)) UUO group as positive control. Haematoxylin & eosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-β1 and α-SMA (P<0.05), whereas HGF increased greatly with AM treatment (P<0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.

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Section: Discussionmentioning

confidence: 99%

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Zuo

Xie

Qiu

et al. 2009

J. Zhejiang Univ. Sci. B

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“…There are reports from experimental studies showing the protective effect of HGF against acute and chronic kidney injury [25-27]. Esposito and co-workers demonstrated that HGF reduced, in in vitro conditions, the expression and synthesis of TGF-beta and collagen type IV in normal human glomeruli [28]. There are also clinical observations suggesting an HGF stimulating effect in recovery of renal function in patients with acute renal failure [15].…”

Section: Discussionmentioning

confidence: 99%

Higher Serum Hepatocyte Growth Factor Concentration is Associated with Better Preservation of GFR in Hemodialysis Patients

Baum

Maćkowiak

Sosińska-Zawierucha

et al. 2017

Kidney Blood Press Res

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Background/Aims: Hemodialysis induces an intravascular inflammatory reaction which may further deteriorate renal function. We studied changes of serum interleukin 6 (IL6) and hepatocyte growth factor (HGF) concentrations during dialysis sessions, and at 12 month intervals. The synthesis of these cytokines in arterial endothelial cells in the presence of serum obtained from dialyzed patients was studied. Changes of the inflammatory reaction during 12 months of treatment were correlated with GFR. Methods: The study was performed on a group of 30 uremic patients treated with hemodialysis. Serum samples were collected before the start of dialysis, 15 minutes, and 4 hours later, when the session was finished. Serum levels of IL6 and HGF were measured with ELISA, as was the effect of serum samples on the synthesis of these cytokines in arterial endothelial cells. Results: At baseline hemodialysis induced an increase of serum IL6 (+10%) and HGF (+164%) levels at the end of the session. After 12 months of treatment predialysis serum IL 6 level was increased as compared to the beginning of the study (+22%), but no change in serum HGF level was observed. At that time the dialysis-induced rise of serum IL6 level was stronger than at the start (+18%), but the observed effect for HGF was weaker (+116%). An inverse correlation was observed between the dialysis-induced increase of HGF level and decrease of GFR after 12 months of study. The same relation was seen for HGF synthesis in the endothelium, but opposite for IL6 synthesis in the endothelium. Conclusions: We found that a higher HGF serum level during hemodialysis treatment is associated with a slower loss of residual renal function.

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“…The activity of metalloproteases was revealed as white bands on the blue-stained gel. The intensity of the bands was measured using an image analyzer as previously reported [15] and results were expressed as the I/R kidney/control kidney ratio.…”

Section: Methodsmentioning

confidence: 99%

“…Membranes were then incubated for 24 h at 4°C with anti-TGF-β antibodies (1:1,000; Santa Cruz Biotechnology, Santa Cruz, Calif., USA) and, after extensive washing, with horseradish peroxidase-conjugated secondary antibodies (1:10,000) for 1 h at room temperature in blocking buffer containing 5% milk. The signals were visualized using enhanced chemiluminescence system and quantified with an image analyzer [15]. β-Actin was used as control.…”

Section: Methodsmentioning

confidence: 99%

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Sirolimus Prevents Short-Term Renal Changes Induced by Ischemia-Reperfusion Injury in Rats

Esposito¹,

Grosjean²,

Torreggiani³

et al. 2011

Am J Nephrol

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Background: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. Methods: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-β, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. Results: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 µl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 µl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-β expression and matrix deposition. Only sirolimus increased metalloprotease activity. Conclusions: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

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Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli

Abstract: HGF reduced expression and synthesis of TGF-beta and collagen type IV and increased MMP-2 mRNA level in normal human glomeruli. These results suggest an antifibrotic effect of HGF on glomerular cells and may explain its beneficial role in glomerulosclerosis.

Cited by 25 publications

References 20 publications

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

Higher Serum Hepatocyte Growth Factor Concentration is Associated with Better Preservation of GFR in Hemodialysis Patients

Sirolimus Prevents Short-Term Renal Changes Induced by Ischemia-Reperfusion Injury in Rats

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