Albumin-stimulated TGF β-1 in renal tubular cells is associated with activation of MAP kinase

Jun Zhao, Alfonso Tramontano, Sudesh P Makker

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Proteinuric renal diseases are often associated with progressive tubulointerstitial fibrosis that usually defines the degree and rate of progression of renal failure. Glomerular filtration of excess albumin, the dominant protein in proteinuria, into proximal tubule could provide the stimulus to induce certain fibrogenic cytokines from proximal tubular cells (PTC), which may account for fibrosis in the interstitium. To explore this hypothesis we tested the effect of bovine albumin in PTC in culture on the expression and secretion of transforming growth factor (TGF) β-1, a prominent fibrogenic cytokine. Methods: TGFβ-1 expressed by cultured PTC was measured by enzyme-linked immunosorbent assay (ELISA) and indirectly by reverse-transcription polymerase chain reaction (RT-PCR). Relative messenger ribonucleic acid (mRNA) levels were measured in ethidium bromides stained gels, by comparison to transcripts for 18s ribosomal RNA. Activated mitogen-activated protein (MAP) kinase was estimated by Western blot with phosphotyrosine-specific antibody. Results: Following incubation of PTC with albumin determination of TGF β-1 mRNA in PTC and TGF β-protein in culture medium both indicated a time- and dose-dependent increase. MAP kinase (p44/42) was activated within 5 min of exposure to albumin. Inhibition of the MAP kinase cascade by PD98059 attenuated the effect of albumin on TGF β-1 expression. Conclusions: These observations suggest that overexpression of TGF β-1 by PTC in response to albumin is regulated through a MAP kinase signaling pathway. This mechanism may play a role in the development of interstitial fibrosis in proteinuric states.

Original languageEnglish (US)
Pages (from-to)1265-1271
Number of pages7
JournalInternational Urology and Nephrology
Volume39
Issue number4
DOIs
StatePublished - Dec 2007

Keywords

  • Glomerular diseases
  • MAP kinase
  • Progressive renal disease
  • Proteinuria
  • TGF β-1
  • Tubulointerstitial fibrosis

ASJC Scopus subject areas

  • Nephrology
  • Urology
  • Geriatrics and Gerontology

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