SPARC regulates TGF-beta1-dependent signaling in primary glomerular mesangial cells

Aleksandar Francki, Timothy D. McClure, Rolf A. Brekken, Kouros Motamed, Carrie Murri, Tongwen Wang, E. Helene Sage

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Secreted protein acidic and rich in cysteine (SPARC), a member of the family of matricellular proteins, regulates the interaction of cells with pleiotropic factors and proteins of the extracellular matrix (ECM). Although it has been appreciated that transforming growth factor beta 1 (TGF-β1) induces SPARC and collagen type I, we have recently shown that SPARC regulates the expression of TGF-β1 and collagen type I in renal mesangial cells via a TGF-β1-dependent pathway, and have proposed a reciprocal, autocrine regulatory feedback loop between SPARC and TGF-β1. Herein, we sought to determine how SPARC regulates TGF-β1-dependent signal transduction. Our data indicate that SPARC modulates the TGF-β1-dependent phosphorylation of Smad-2 in primary mesangial cells derived from wild-type and SPARC-null mice. We also show that SPARC regulates the levels and activation of the stress-activated c-jun-N-terminal kinase (JNK) in mesangial cells by augmentation of the stimulatory effects of TGF-β1. Furthermore, we found that SPARC increases the levels and the activity of the transcription factor c-jun. These effects of SPARC on the TGF-β1 signaling pathway appear to be mediated through an interaction with the TGF-β1-receptor complex, but only in the presence of TGF-β1 bound to its cognate type II receptor. That SPARC is directly involved in the regulation of the TGF-β1 signaling cascade is consistent with the paradigm that matricellular proteins modulate interactions among cells, growth factors, and their respective receptors.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalJournal of Cellular Biochemistry
Volume91
Issue number5
DOIs
StatePublished - 2004

Keywords

  • JNK
  • Matricellular
  • Mesangial cells
  • Receptor interactions
  • SPARC
  • Smad
  • TGF-β
  • Transcription factors
  • c-jun

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'SPARC regulates TGF-beta1-dependent signaling in primary glomerular mesangial cells'. Together they form a unique fingerprint.

Cite this