TGF-β1 stimulates cyclooxygenase-2 expression and PGE 2 production of human dental pulp cells: Role of ALK5/Smad2 and MEK/ERK signal transduction pathways

Lin, Po-Shuen; Cheng, Ru-Hsiu; Chang, Mei‐Chi; Lee, Jang‐Jaer; Chang, Hung‐Hao; Huang, Weiling; Yeung, Sin‐Yuet; Chang, Ya-Ching; Jeng, Jiiang‐Huei

doi:10.1016/j.jfma.2017.07.008

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…11,33,38 Smad3 is a downstream target of ALK5 and may be a final target in the TGFβ-TGFβRII-ALK5-Smad3 signaling pathway. 9,39 If ALK5/Smad3 can be activated only by TGFβ, ALK5/Smad3 should theoretically be involved in analgesia at the central level; however, our findings are not consistent with this conclusion. One key to solving this problem may be to determine whether ALK5 is involved in the modulation of pain at the central level and likewise to determine whether the non-canonical Smad3 signaling pathway is also dependent on ALK5 activation.…”

contrasting

confidence: 80%

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

Peng

Chen

et al. 2020

JPR

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The chemokine receptor, CXCR4, and the transforming growth factor-beta receptor, ALK5, both contribute to various processes associated with the sensation of pain. However, the relationship between CXCR4 and ALK5 and the possible mechanisms promoted by ALK5 in the development of pain have not been evaluated. Materials and Methods: Tumor cell implantation (TCI) technology was used to generate a model of cancer-induced bone pain (CIBP) in rats; intrathecal (i.t.) injections of small interfering (si) RNAs targeting CXCR4 and the ALK5-specific inhibitor, RepSox, were performed. Behavioral outcomes, Western blotting, and immunofluorescence techniques were used to evaluate the expression of the aforementioned specific target proteins in the CIBP model. Results: The results revealed that i.t. administration of siRNAs targeting CXCR4 resulted in significant reductions in both mechanical and thermal hyperalgesia in rats with CIBP and likewise significantly reduced the expression of ALK5 in the spinal cord. Similarly, i.t. administration of RepSox also resulted in significant reductions in mechanical and thermal hyperalgesia in rats with CIBP together with diminished levels of spinal p-Smad3. Conclusion: Taken together, our results suggest that CXCR4 expression in the spinal cord may be a critical mediator of CIBP via its capacity to activate ALK5 and downstream signaling pathways.

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contrasting

confidence: 80%

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

Peng

Chen

et al. 2020

JPR

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“…The results demonstrated that TGF-β1 induced M2-polarization of macrophages in a concentration-dependent manner. Since a number of studies have demonstrated that COX-2 can be induced by TGF-β1 (19,37), the present study aimed to determine whether the TGF-β1/COX-2 pathway also had a role in OKC. The results of the present study indicated that COX-2 was upregulated by TGF-β1 in a concentration-dependent manner and that a high expression was observed in OKC-induced M2-polarization of macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…COX exists as two isoforms: COX-1 and COX-2. COX-1 is universally expressed in high concentrations, whereas COX-2 is expressed in low concentrations but can be induced by multiple stimuli (19,23). In the present study, the expression levels of the two genes were quantified in response to different treatments.…”

Section: Tgf-β1 Is Upregulated In M2-polarized Macrophages Treated Wimentioning

confidence: 96%

“…In addition, COX-2 is generally absent or at very low levels in cells, but can be induced by pro-inflammatory and mitogenic stimuli (17,18). Transforming growth factor (TGF)-β1 is an important growth factor which performs various roles in biological growth and development (19). A previous study suggested that TGF-β1 may upregulate the expression of COX-2 in the early stages of human dental pulp inflammation (19); thus indicating that TGF-β1-induced COX-2 expression may serve an important role in human dental disease.…”

Section: The Tgf-β1/cox-2-dependant Pathway Serves a Key Role In The mentioning

confidence: 99%

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The TGF‑β1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis

et al. 2020

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An odontogenic keratocyst (OKC) is a common oral cyst arising from the odontogenic epithelium, which has the characteristics of a tumor. Previous studies have demonstrated that M2-polarized macrophages and angiogenesis have important roles in the progression of OKCs. As transforming growth factor (TGF)-β1 is important in growth and developmental processes, and early studies have indicated that TGF-β1 is upregulated in OKCs, the present study aimed to investigate the expression levels of TGF-β1 as a first step. Flow cytometric analysis suggested that TGF-β1 induced M2-polarization of macrophages in a dose-dependent manner. Expression levels of cyclooxygenase (COX)-1 and-2 were measured after treatment of M2 macrophages with TGF-β1 and OKC homogenate supernatant. COX-2 expression was influenced by TGF-β1 in a concentration-dependent manner and in OKC induction. In addition, inhibition of COX-2 resulted in the induction of M2-polarization of macrophages via TGF-β1 and OKC disruption. Because the extracellular matrix (ECM) is altered in individuals with chronic diseases, the present study analyzed the expression of matrix metalloproteinase (MMP)-9, which is able to degrade the ECM. The present study observed a decrease in MMP-9 activity following treatment with TGF-β1 and OKC homogenate supernatant. Additionally, the present study analyzed tube formation caused by OKC with or without a COX-2 inhibitor. The results of the present study suggested that angiogenesis increased following treatment with OKC homogenate supernatant but decreased after treatment with a COX-2 inhibitor. These findings indicated that the TGF-β1/COX-2 pathway may have an important role in the progression of OKC.

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“…In recent studies, it has been assumed that TGF-β and VEGF are involved in the evolution of the immune response in periodontal disease and caries [ 13 , 14 ]. Our patient had many untreated dental caries with apical periodontitis at the onset of JLS, and healthy permanent teeth gradually replaced them.…”

Section: Discussionmentioning

confidence: 99%

Juvenile Localized Scleroderma with Hyaline Deposits in the Renal Arteriole

Tabata

Inoue

2018

Case Rep Dermatol

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We report a 10-year-old boy with localized scleroderma of the linear and plaque type, who showed proteinuria and hematuria. In this patient, skin, articular, and renal manifestations appeared successively and then began to resolve in the same order. A renal biopsy specimen demonstrated mild mesangial cell proliferation, exudate of immunoglobulin in the glomerular capillary, and large electron-dense deposits in the afferent arteriole. We consider that there were some transient factors that had caused the skin and articular manifestations, which also induced renal vascular inflammatory responses.

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TGF-β1 stimulates cyclooxygenase-2 expression and PGE 2 production of human dental pulp cells: Role of ALK5/Smad2 and MEK/ERK signal transduction pathways

Abstract: TGF-β1 increased the COX-2 and PGE level of cultured pulp cells. The effect of TGF-β1 on COX-2 protein expression was associated with ALK5/Smad2/3 and MEK/ERK pathways. These events are important in the early inflammation, repair and regeneration of dental pulp in response to injury.

Cited by 13 publications

References 44 publications

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

The TGF‑β1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis

Juvenile Localized Scleroderma with Hyaline Deposits in the Renal Arteriole

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TGF-β1 stimulates cyclooxygenase-2 expression and PGE 2 production of human dental pulp cells: Role of ALK5/Smad2 and MEK/ERK signal transduction pathways

Abstract: TGF-β1 increased the COX-2 and PGE level of cultured pulp cells. The effect of TGF-β1 on COX-2 protein expression was associated with ALK5/Smad2/3 and MEK/ERK pathways. These events are important in the early inflammation, repair and regeneration of dental pulp in response to injury.

Cited by 13 publications

References 44 publications

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

<p>Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain</p>

The TGF‑&beta;1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis

Juvenile Localized Scleroderma with Hyaline Deposits in the Renal Arteriole

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The TGF‑β1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis