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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.

ABSTRACT: 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.

SUBMITTER: Cheng G

PROVIDER: S-EPMC7416411 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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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.

Cheng Gang G Gao Jinxing J Wang Lianfei L Ding Yude Y Wu Qian Q Wang Quanbing Q Xiao Jialing J Wang Shibing S

Oncology letters 20200723 4

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 a ...[more]

PMID: 32788934

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Project description:BackgroundMelatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms.Materials and methodsMEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-β1 (TGF-β1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-β1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed.ResultsIn vitro, we found that TGF-β1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-β1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis.ConclusionMelatonin attenuates bladder fibrosis by blocking the TGF-β1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

Dataset Information

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

Publications

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

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