Transforming growth factor-β modulation of the αl (IV) collagen gene in marine proximal tubular cells

Gerald S. Kuncio*, Rene Alvarez, L. I. Shaoran, Paul D. Killen, Eric G. Neilson

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We have examined the expression of the αl(IV) collagen gene in murine proximal tubular cells (MCT) to better understand how it is regulated in parenchymal cells. Transcriptional activity was examined using luciferase reporters driven by the αl(IV) promoter and varying lengths of 5′-flanking sequences. The minimal bidirectional promoter showed low intrinsic activity in MCT cells, but addition of upstream sequences increased luciferase expression. Maximal activity resided within the first 1,200 bp upstream. A minigene construct was generated by placing a portion of the αl(IV) first intron downstream from the promoter region. The intronic sequences significantly decreased activity of the promoter in MCT cells and 3T3 fibroblasts but greatly enhanced expression in murine parietal yolk sac (PYS) endodermal cells. Addition of transforming growth factor-β (TGF-β) to MCT cultures elevated the levels of secreted type IV collagen. Treatment of either transiently or stably transfected MCT cells with TGF-β produced an increase in the levels of expression of all of the reporters tested. These data support the hypothesis that cell-specific regulation of αl(IV) collagen is dependent upon downstream sequences, which act to decrease the expression of type IV collagen in tubular epithelium. The activity of the αl(IV) collagen gene in proximal tubular cells is increased by TGF-β, which acts on the domain(s) embedded within the intergenic bidirectional promoter.

Original languageEnglish (US)
Pages (from-to)F120-F125
JournalAmerican Journal of Physiology
Volume271
Issue number1 PART 2
StatePublished - 1996

Keywords

  • Collagen
  • Cytokines
  • Gene expression
  • Transcription

ASJC Scopus subject areas

  • Physiology (medical)

Fingerprint Dive into the research topics of 'Transforming growth factor-β modulation of the αl (IV) collagen gene in marine proximal tubular cells'. Together they form a unique fingerprint.

  • Cite this