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Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts.

ABSTRACT: Abnormal transforming growth factor-beta (TGF-beta) signaling is a critical contributor to the pathogenesis of various human diseases ranging from tissue fibrosis to tumor formation. Excessive TGF-beta signaling stimulates fibrotic responses. Recent research has focused in the main on the antiproliferative effects of TGF-beta in fibroblasts, and it is presently understood that TGF-beta-stimulated cyclooxygenase-2 (COX-2) induction in fibroblasts is essential for antifibroproliferative effects of TGF-beta. Both TGF-beta and COX-2 have been implicated in tumor growth, invasion, and metastasis, and therefore tumor-associated fibroblasts are a recent topic of interest. Here we report the identification of positive and negative regulatory factors of COX-2 expression induced by TGF-beta as determined using proteomic approaches. We show that TGF-beta coordinately up-regulates three factors, heterogeneous nuclear ribonucleoprotein A/B (HNRPAB), nucleotide diphosphate kinase A (NDPK A), and nucleotide diphosphate kinase A (NDPK B). Functional pathway analysis showed that HNRPAB augments mRNA and protein levels of COX-2 and subsequent prostaglandin E(2) (PGE(2)) production by suppressing degradation of COX-2 mRNA. In contrast, NDPK A and NDPK B attenuated mRNA and protein levels of COX-2 by affecting TGF-beta-Smad2/3/4 signaling at the receptor level. Collectively, we report on a new regulatory pathway of TGF-beta in controlling expression of COX-2 in fibroblasts, which advances our understanding of pathophysiological mechanisms of TGF-beta.

SUBMITTER: Matsumura T

PROVIDER: S-EPMC2791015 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts.

Matsumura Takayoshi T Suzuki Toru T Aizawa Kenichi K Sawaki Daigo D Munemasa Yoshiko Y Ishida Junichi J Nagai Ryozo R

The Journal of biological chemistry 20091201 51

Abnormal transforming growth factor-beta (TGF-beta) signaling is a critical contributor to the pathogenesis of various human diseases ranging from tissue fibrosis to tumor formation. Excessive TGF-beta signaling stimulates fibrotic responses. Recent research has focused in the main on the antiproliferative effects of TGF-beta in fibroblasts, and it is presently understood that TGF-beta-stimulated cyclooxygenase-2 (COX-2) induction in fibroblasts is essential for antifibroproliferative effects of ...[more]

PMID: 19837676

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Dataset Information

Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts.

Publications

Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts.

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