Effects of Dibutyryl Cyclic AMP on Hyaluronan and Proteoglycan Synthesis by Retroocular Tissue Fibrobrasts in Culture.

Imai, Yumi; Ibaraki, Kyomi; Odajima, Ritsuko; Shishiba, Yoshimasa

doi:10.1507/endocrj.41.645

Cited by 17 publications

(9 citation statements)

References 19 publications

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“…Bt 2 cAMP synergistically enhanced expression of both HAS2 mRNA and HA protein when coincubated with TGF-␤. Although it is well established that artificial cAMP stimulators can stimulate HA synthesis in various cell types (73)(74)(75), we are unaware of any studies addressing the combinatory effect of these agents with TGF-␤. Computational analysis of the regulatory elements of HAS2 identified three CREB-and seven Smad-binding sites within the 5Ј promoter region.…”

Section: Discussionmentioning

confidence: 99%

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

Schiller

Dennler

Anderegg

et al. 2010

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

Schiller

Dennler

Anderegg

et al. 2010

Journal of Biological Chemistry

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“…PKC and PKA signal transduction pathways may be involved in activating HA synthesis [Honda et al, 1993;Imai et al, 1994;Klews and Prehm, 1994;Suzuki et al, 1995]. The effects of the PKA inhibitor H-89 on HA synthesis in fibroblasts treated with TGF-b and PMA are particularly interesting.…”

Section: Discussionmentioning

confidence: 99%

“…HA synthesis can be inhibited by TGF-b1 in human rheumatoid fibroblasts [Kawakami et al, 1998]. PKC [Klews and Prehm, 1994;Suzuki et al, 1995] or c-AMP dependent protein kinases [Honda et al, 1993;Imai et al, 1994;Klews and Prehm, 1994;Suzuki et al, 1995] may be involved in activating HA synthesis. TGF-b activates various serine/threonine kinases [Massague, 1996;Massague and Weis-Garcia, 1996] as well as a number of PKA pathways ].…”

mentioning

confidence: 99%

TGF‐β induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C βII activation in vitro

Wang¹,

Tung²,

Tang

et al. 2005

J of Cellular Biochemistry

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Graves' ophthalmopathy is accompanied by hyaluronan (HA) accumulation in the orbital space and infiltration of immunocompetent cells and cytokines, including IFN-gamma, IL-1beta, and TGF-beta. We examined the signal transduction pathways by which TGF-beta induces HA synthesis in normal orbital fibroblasts, orbital fibroblasts from patients with Graves' ophthalmopathy, and abdominal fibroblasts. Calphostin C inhibited the stimulation of HA synthesis by TGF-beta. Phorbol 12-myristate 13-acetate (PMA) activation of PKC stimulated HA production. The effects of TGF-beta and PMA were not synergistic. Stimulation by TGF-beta and PMA were dependent on protein synthesis and their effects were inhibited by cycloheximide. Since TGF-beta-induced HA synthesis was inhibited by BAPTA or by PKC inhibitors, a calcium-dependent PKC was most likely involved. The PKA inhibitor H-89 enhanced TGF-beta- and PMA-induced HA synthesis, thus showing that communication between the PKA and PKC pathways was evident. TGF-beta stimulated the translocation of PKCbetaII to the cell membrane. PKCbetaII, a key enzyme in the regulation of HA synthesis by TGF-beta, might be an appropriate target for therapeutic compounds to be used to treat Graves' ophthalmopathy accompanied by inflammation.

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“…Two signal transduction pathways, involving PKC [Klewes and Prehm, 1994;Suzuki et al, 1995] or cAMP dependent protein kinases [Honda et al, 1993;Klewes and Prehm, 1994;Imai et al, 1994;Suzuki et al, 1995], have been suggested to be involved in activating hyaluronan synthesis. Here, we show that both IL-1b and PMA can stimulate hyaluronan synthesis in orbital ®broblasts.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of hyaluronan synthesis by interleukin‐1β involves activation of protein kinase C βII in fibroblasts from patients with Graves' ophthalmopathy

Wong¹,

Tang²,

Wu³

et al. 2001

J of Cellular Biochemistry

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Hyaluronan accumulation in the retroorbital connective tissue is one of the pathological features of Graves' ophthalmopathy. Interleukin-1beta (IL-1beta) is known to stimulate hyaluronan synthesis in orbital fibroblasts. In the present study, the intracellular signal transduction pathways involved in this stimulatory effect were investigated in cultured human retroorbital fibroblasts from patients with Graves' ophthalmopathy. IL-1beta-induced hyaluronan synthesis was significantly inhibited by pretreatment of the cells with two protein kinase C (PKC) inhibitors, chlerythrine chloride and H-7. In addition, treatment with phorbol 12-myristate 13-acetate (PMA), a direct PKC activator, also resulted in increased hyaluronan production. IL-1beta- or PMA-stimulated hyaluronan synthesis was blocked by the protein synthesis inhibitor, cycloheximide. Moreover, the intracellular Ca(2+) concentration of the orbital fibroblasts was also involved in the IL-1beta induced transduction pathway, the effect being completely inhibited by BAPTA, an internal calcium chelator. In addition, A23187, a calcium ionophore, increased hyaluronan synthesis in unstimulated cells. These results suggest that the Ca(2+)-dependent PKC signal transduction pathway plays an important role in the IL-1beta-induced hyaluronan synthesis. Moreover, IL-1beta treatment resulted in increased PKC activity and the rapid translocation of PKC betaII from the cytoplasm to the plasma membrane. These results indicate that cytosolic Ca(2+) and PKC betaII are involved in IL-1beta-induced hyaluronan synthesis in cultured orbital fibroblasts from patients with Graves' ophthalmopathy.

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Effects of Dibutyryl Cyclic AMP on Hyaluronan and Proteoglycan Synthesis by Retroocular Tissue Fibrobrasts in Culture.

Cited by 17 publications

References 19 publications

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

Increased cAMP Levels Modulate Transforming Growth Factor-β/Smad-induced Expression of Extracellular Matrix Components and Other Key Fibroblast Effector Functions

TGF‐β induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C βII activation in vitro

Stimulation of hyaluronan synthesis by interleukin‐1β involves activation of protein kinase C βII in fibroblasts from patients with Graves' ophthalmopathy

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