A nuclear protein in mesangial cells that binds to the promoter region of the platelet-derived growth factor-A chain gene: Induction by phorbol ester

B. Bhandari, U. O. Wenzel, F. Marra, H. E. Abboud

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Mesangial cells predominantly express platelet-derived growth factor (PDGF)-A chain mRNA and release PDGF. Mesangial cell PDGF-A chain mRNA abundance is regulated by several agents including phorbol esters. We have recently demonstrated that induction of PDGF-A chain mRNA abundance in response to phorbol 12-myristate 13-acetate is primarily due to gene transcription. We have now analyzed the 5'-flanking region of the PDGF-A chain promoter to identify DNA binding protein(s) which have the potential to regulate PDGF-A chain gene transcription in human mesangial cells. DNase I footprint analysis of the 5'-flanking region of the PDGF-A chain promoter identifies a DNase I protected region at the location -82 to -102 corresponding to the sequence 5'-GGCCCGGAATCCGGGGGAGGC-3'. Therefore, nuclear extracts from human mesangial cells contain a protein, PDGF-A-BP-1, that binds to a DNA sequence (-82 to -102) in the promoter region of the PDGF-A chain gene. Gel mobility shift analysis using labeled oligomer corresponding to the binding site for PDGF-A-BP-1 indicates that PDGF-A-BP-1 is induced by phorbol ester in mesangial cells as well as fat-storing cells (>20 fold). Egr-1 protein does not bind to labeled PDGF-A-BP-1 oligomer and does not compete with the binding of PDGF-A-BP-1. In addition, SP-1 binding sequence does not compete with the binding sequence of the mesangial cell protein. PDGF-A-BP-1 appears to represent a novel protein which is induced by phorbol ester and thus has the potential for an important role in the transcriptional regulation of the PDGF-A chain gene in mesangial cells and other vascular pericytes.

Original languageEnglish (US)
Pages (from-to)5541-5548
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number10
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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