Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro

G. M. Ghiggeri, P. Altieri, R. Oleggini, F. Ginevri, G. Candiano, A. Garberia, G. Fabbretti, F. Perfumo, R. Gusmano

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Chronic Adriamycin® (ADR) nephropathy is invariably associated with glomerulosclerosis and tubulointerstitial fibrosis. To investigate the hypothesis that severe albuminuria plays a role in the pathogenesis of both processes we purified the protein from conditioned media of rats with advanced ADR nephropathy and tested the fibrogenic effect on renal fibroblasts and mesangial cells in vitro. Albumin was purified by pseudoligand chromatography and was identified on the basis of the NH(z) amino terminus. Furthermore, it was differentiated from the urinary homologue, being more anionic and more fatted while maintaining a conserved peptide composition. The exposure of renal cells to renal albumin induced a dose-dependent reduction in collagen synthesis with a half-maximal decrease with 0.2 μg/ml of albumin. With renal albumin levels of 0.4 μg/ml the collagen incorporation of 3H-proline by mesangial cells and renal fibroblasts (primary cultures and cell lines) was reduced by 76, 81 and 45% respectively. A qualitative analysis by SDS-polyacrylamide electrophoresis and immunoprecipitation of radiolabelled collagens demonstrated a drastic and unselective decrease in all major collagens synthesized by mesangial cells and fibroblasts, including type I, III and V. Previous immunoprecipitation of the protein with anti-rat albumin antibodies completely reversed this phenomenon. Finally, albumin purified from urines of rats with ADR nephropathy downregulated the synthesis by renal cells of the same collagens but this effect was less evident compared to renal albumin. These findings demonstrate that renal albumin drastically reduces the synthesis of collagens by mesangial cells and renal fibroblasts, this effect being most evident on those components which constitute the extracellular matrix in glomerulosclerosis and interstitial fibrosis. We hypothesize that renal albumin per se protects rather than aggravates renal pathology in models of progressive renal disease.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalNephron
Volume68
Issue number3
Publication statusPublished - 1994

Fingerprint

Glomerular Mesangium
Mesangial Cells
Albumins
Down-Regulation
Fibroblasts
Kidney
Collagen
Doxorubicin
Immunoprecipitation
Fibrosis
In Vitro Techniques
Albuminuria
Conditioned Culture Medium
Proline
Extracellular Matrix
Electrophoresis
Chromatography
Proteins
Urine

Keywords

  • Adriamycin®
  • Albumin
  • Experimental nephrosis
  • Extracellular matrix
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology

Cite this

Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro. / Ghiggeri, G. M.; Altieri, P.; Oleggini, R.; Ginevri, F.; Candiano, G.; Garberia, A.; Fabbretti, G.; Perfumo, F.; Gusmano, R.

In: Nephron, Vol. 68, No. 3, 1994, p. 353-359.

Research output: Contribution to journalArticle

Ghiggeri, GM, Altieri, P, Oleggini, R, Ginevri, F, Candiano, G, Garberia, A, Fabbretti, G, Perfumo, F & Gusmano, R 1994, 'Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro', Nephron, vol. 68, no. 3, pp. 353-359.
Ghiggeri, G. M. ; Altieri, P. ; Oleggini, R. ; Ginevri, F. ; Candiano, G. ; Garberia, A. ; Fabbretti, G. ; Perfumo, F. ; Gusmano, R. / Intact renal albumin downregulates the extracellular matrix expression by mesangial cells and renal fibroblasts in vitro. In: Nephron. 1994 ; Vol. 68, No. 3. pp. 353-359.
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AU - Candiano, G.

AU - Garberia, A.

AU - Fabbretti, G.

AU - Perfumo, F.

AU - Gusmano, R.

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AB - Chronic Adriamycin® (ADR) nephropathy is invariably associated with glomerulosclerosis and tubulointerstitial fibrosis. To investigate the hypothesis that severe albuminuria plays a role in the pathogenesis of both processes we purified the protein from conditioned media of rats with advanced ADR nephropathy and tested the fibrogenic effect on renal fibroblasts and mesangial cells in vitro. Albumin was purified by pseudoligand chromatography and was identified on the basis of the NH(z) amino terminus. Furthermore, it was differentiated from the urinary homologue, being more anionic and more fatted while maintaining a conserved peptide composition. The exposure of renal cells to renal albumin induced a dose-dependent reduction in collagen synthesis with a half-maximal decrease with 0.2 μg/ml of albumin. With renal albumin levels of 0.4 μg/ml the collagen incorporation of 3H-proline by mesangial cells and renal fibroblasts (primary cultures and cell lines) was reduced by 76, 81 and 45% respectively. A qualitative analysis by SDS-polyacrylamide electrophoresis and immunoprecipitation of radiolabelled collagens demonstrated a drastic and unselective decrease in all major collagens synthesized by mesangial cells and fibroblasts, including type I, III and V. Previous immunoprecipitation of the protein with anti-rat albumin antibodies completely reversed this phenomenon. Finally, albumin purified from urines of rats with ADR nephropathy downregulated the synthesis by renal cells of the same collagens but this effect was less evident compared to renal albumin. These findings demonstrate that renal albumin drastically reduces the synthesis of collagens by mesangial cells and renal fibroblasts, this effect being most evident on those components which constitute the extracellular matrix in glomerulosclerosis and interstitial fibrosis. We hypothesize that renal albumin per se protects rather than aggravates renal pathology in models of progressive renal disease.

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