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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background. The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli. Methods. Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (α2) IV collagen, transforming growth factor-β (TGF-β), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). β-actin was used as housekeeping gene. The production of collagen type IV and TGF-β was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography. Results. (α2) IV collagen, TGF-β, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-β. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion. Conclusion. HGF reduced expression and synthesis of TGF-β 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.

Original languageEnglish
Pages (from-to)2143-2150
Number of pages8
JournalKidney International
Volume67
Issue number6
DOIs
Publication statusPublished - Jun 2005

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Hepatocyte Growth Factor
Transforming Growth Factors
Matrix Metalloproteinases
Collagen Type IV
Metalloproteases
Messenger RNA
Collagen
Kidney
Biopsy
Matrix Metalloproteinase Inhibitors
Essential Genes
Chronic Kidney Failure
Renal Insufficiency
Extracellular Matrix
Culture Media
Actins
Transplantation
Western Blotting
Enzyme-Linked Immunosorbent Assay
Light

Keywords

  • Fibrosis
  • Glomeruli
  • HGF
  • TGF-β

ASJC Scopus subject areas

  • Nephrology

Cite this

Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli. / Esposito, Ciro; Parrilla, Bina; De Mauri, Andreana; Cornacchia, Flavia; Fasoli, Gianluca; Foschi, Annalisa; Mazzullo, Tiziana; Plati, AnnaRita; Scudellaro, Roberta; Dal Canton, Antonio.

In: Kidney International, Vol. 67, No. 6, 06.2005, p. 2143-2150.

Research output: Contribution to journalArticle

Esposito, C, Parrilla, B, De Mauri, A, Cornacchia, F, Fasoli, G, Foschi, A, Mazzullo, T, Plati, A, Scudellaro, R & Dal Canton, A 2005, 'Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli', Kidney International, vol. 67, no. 6, pp. 2143-2150. https://doi.org/10.1111/j.1523-1755.2005.00319.x
Esposito, Ciro ; Parrilla, Bina ; De Mauri, Andreana ; Cornacchia, Flavia ; Fasoli, Gianluca ; Foschi, Annalisa ; Mazzullo, Tiziana ; Plati, AnnaRita ; Scudellaro, Roberta ; Dal Canton, Antonio. / Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli. In: Kidney International. 2005 ; Vol. 67, No. 6. pp. 2143-2150.
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abstract = "Background. The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli. Methods. Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (α2) IV collagen, transforming growth factor-β (TGF-β), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). β-actin was used as housekeeping gene. The production of collagen type IV and TGF-β was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography. Results. (α2) IV collagen, TGF-β, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-β. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion. Conclusion. HGF reduced expression and synthesis of TGF-β 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.",
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AU - Parrilla, Bina

AU - De Mauri, Andreana

AU - Cornacchia, Flavia

AU - Fasoli, Gianluca

AU - Foschi, Annalisa

AU - Mazzullo, Tiziana

AU - Plati, AnnaRita

AU - Scudellaro, Roberta

AU - Dal Canton, Antonio

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AB - Background. The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli. Methods. Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (α2) IV collagen, transforming growth factor-β (TGF-β), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). β-actin was used as housekeeping gene. The production of collagen type IV and TGF-β was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography. Results. (α2) IV collagen, TGF-β, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-β. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion. Conclusion. HGF reduced expression and synthesis of TGF-β 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.

KW - Fibrosis

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