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Distinct involvement of the Jun-N-terminal kinase and NF-kappaB pathways in the repression of the human COL1A2 gene by TNF-alpha.: JNK- and NF-kB-driven repression of COL1A2 expression

Abstract : We used a gene knockout approach to elucidate the specific roles played by the Jun-N-terminal kinase (JNK) and NF-kappaB pathways downstream of TNF-alpha in the context of alpha(2) type I collagen gene (COL1A2) expression. In JNK1-/--JNK2-/- (JNK-/-) fibroblasts, TNF-alpha inhibited basal COL1A2 expression but had no effect on TGF-beta-driven gene transactivation unless jnk1 was introduced ectopically. Conversely, in NF-kappaB essential modulator-/- (NEMO-/-) fibroblasts, lack of NF-kappaB activation did not influence the antagonism exerted by TNF-alpha against TGF-beta but prevented repression of basal COL1A2 gene expression. Similar regulatory mechanisms take place in dermal fibroblasts, as evidenced using transfected dominant-negative forms of MKK4 and IKK-alpha, critical kinases upstream of the JNK and NF-kappaB pathways, respectively. These results represent the first demonstration of an alternate usage of distinct signaling pathways by TNF-alpha to inhibit the expression of a given gene, COL1A2, depending on its activation state.
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https://www.hal.inserm.fr/inserm-00147463
Contributor : Alain Mauviel <>
Submitted on : Monday, May 21, 2007 - 3:02:28 PM
Last modification on : Monday, May 21, 2007 - 3:02:28 PM
Long-term archiving on: : Thursday, April 8, 2010 - 4:58:44 PM

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Franck Verrecchia, Erwin Wagner, Alain Mauviel. Distinct involvement of the Jun-N-terminal kinase and NF-kappaB pathways in the repression of the human COL1A2 gene by TNF-alpha.: JNK- and NF-kB-driven repression of COL1A2 expression. EMBO Reports, EMBO Press, 2002, 3 (11), pp.1069-74. ⟨10.1093/embo-reports/kvf219⟩. ⟨inserm-00147463⟩

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