Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Tarek Abd El Kader, Satoshi Kubota, Danilo Janune, Takashi Nishida, Takako Hattori, Eriko Aoyama, Bernard Perbal, Takuo Kuboki, Masaharu Takigawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

CCN family proteins 2 and 3 (CCN2 and CCN3) belong to the CCN family of proteins, all having a high level of structural similarity. It is widely known that CCN2 is a profibrotic molecule that mediates the development of fibrotic disorders in many different tissues and organs. In contrast, CCN3 has been recently suggested to act as an anti-fibrotic factor in several tissues. This CCN3 action was shown earlier to be exerted by the repression of the CCN2 gene expression in kidney tissue, whereas different findings were obtained for liver cells. Thus, the molecular action of CCN3 yielding its anti-fibrotic effect is still controversial. Here, using a general model of fibrosis, we evaluated the effect of CCN3 overexpression on the gene expression of all of the CCN family members, as well as on that of fibrotic marker genes. As a result, repression of CCN2 gene expression was modest, while type I collagen and α-smooth muscle actin gene expression was prominently repressed. Interestingly, not only CCN2, but also CCN4 gene expression showed a decrease upon CCN3 overexpression. These findings indicate that fibrotic gene induction is under the control of a complex molecular network conducted by CCN family members functioning together.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalJournal of Cell Communication and Signaling
Volume7
Issue number1
DOIs
Publication statusPublished - Mar 1 2013

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Keywords

  • CCN family
  • CCN2
  • CCN3
  • CCN4
  • Fibrosis
  • NOV

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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