WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death

Kaliyamurthi Venkatachalam, Balachander Venkatesan, Anthony J. Valente, Peter Melby, Sailesh Nandish, Jane E B Reusch, Robert A. Clark, Bysani Chandrasekar

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

WNT1-inducible signaling pathway protein-1 (WISP1), a member of the CYR61/CTGF/Nov family of growth factors, can mediate cell growth, transformation, and survival. Previously we demonstrated that WISP1 is up-regulated in post-infarct heart, stimulates cardiac fibroblast proliferation, and is induced by the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Here we investigated (i) the localization of TNF-α and WISP1 in post-infarct heart, (ii) the mechanism of TNF-α-mediated WISP1 induction in primary human cardiac fibroblasts (CF), (iii) the role of WISP1 in TNF-α-mediated CF proliferation and collagen production, and (iv) the effects of WISP1 on TNF-α-mediated cardiomyocyte death. TNF-α and WISP1 expressions were increased in the border zones and nonischemic remote regions of the post-ischemic heart. In CF, TNF-α potently induced WISP1 expression in cyclic AMP response element-binding protein (CREB)-dependent manner. TNF-α induced CREB phosphorylation in vitro and DNA binding and reporter gene activities in vivo. TNF-α induced CREB activation via ERK1/2, and inhibition of ERK1/2 and CREB blunted TNF-α-mediated WISP1 induction. Most importantly, WISP1 knockdown attenuated TNF-α stimulated collagen production and CF proliferation. Furthermore, WISP1 attenuated TNF-α-mediated cardiomyocyte death, thus demonstrating pro-mitogenic and pro-survival effects for WISP1 in myocardial constituent cells. Our results suggest that a TNF-α/WISP1 signaling pathway may contribute to post-infarct cardiac remodeling, a condition characterized by fibrosis and progressive cardiomyocyte loss.

Original languageEnglish (US)
Pages (from-to)14414-14427
Number of pages14
JournalJournal of Biological Chemistry
Volume284
Issue number21
DOIs
StatePublished - May 22 2009
Externally publishedYes

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Fibroblasts
Cardiac Myocytes
Tumor Necrosis Factor-alpha
Survival
Proteins
Cyclic AMP Response Element-Binding Protein
Collagen
Phosphorylation
Cell growth
Reporter Genes
Intercellular Signaling Peptides and Proteins
Fibrosis
Genes
Chemical activation
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death. / Venkatachalam, Kaliyamurthi; Venkatesan, Balachander; Valente, Anthony J.; Melby, Peter; Nandish, Sailesh; Reusch, Jane E B; Clark, Robert A.; Chandrasekar, Bysani.

In: Journal of Biological Chemistry, Vol. 284, No. 21, 22.05.2009, p. 14414-14427.

Research output: Contribution to journalArticle

Venkatachalam, Kaliyamurthi ; Venkatesan, Balachander ; Valente, Anthony J. ; Melby, Peter ; Nandish, Sailesh ; Reusch, Jane E B ; Clark, Robert A. ; Chandrasekar, Bysani. / WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 21. pp. 14414-14427.
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AU - Venkatachalam, Kaliyamurthi

AU - Venkatesan, Balachander

AU - Valente, Anthony J.

AU - Melby, Peter

AU - Nandish, Sailesh

AU - Reusch, Jane E B

AU - Clark, Robert A.

AU - Chandrasekar, Bysani

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