TCDD inhibited the osteogenic differentiation of human fetal palatal mesenchymal cells through AhR and BMP-2/TGF-β/Smad signaling

Liu, Xiaozhuan; Li, Xue; Tao, Yuchang; Li, Ning; Ji, Mengmeng; Zhang, Xiuli; Chen, Yao; He, Zhidong; Yu, Kai-Lun; Yu, Zengli

doi:10.1016/j.tox.2019.152353

Cited by 21 publications

(22 citation statements)

References 51 publications

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“…Cleft palate, a common craniofacial birth defect, occurs when there is failure to generate the intact palate separating the nasal cavity from the oral cavity (Iwata et al, 2012); this abnormality is caused by the interaction of genetic and environmental factors. The murine secondary palates initially erupt from the bilateral maxillary processes at embryonic day 11.5 (E11.5), grow vertically flanking the developing tongue (E11.5–13.5), and subsequently reorient above the dorsum of tongue to contact each other and fuse (E13.5–15.5) (Li, Lan, & Jiang, 2017; Liu et al, 2020). Over 90% of the cleft palate caused by the disruption of elevating process (Kai & Ornitz, 2011).…”

Section: Introductionmentioning

confidence: 99%

Lithium‐induced overexpression of β‐catenin delays murine palatal shelf elevation by Cdc‐42 mediated F‐actin remodeling in mesenchymal cells

Wang

Liu

et al. 2020

Birth Defects Research

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Background Lithium chloride (LiCl) is widely used for the treatment of manic and other psychotic disorders, but the administration of lithium can result in several congenital defects in the fetus, including cleft palate (Meng, Wang, Torensma, Jw & Bian, 2015) (Szabo, 1970). However, the mechanism of Lithium's action as a developmental toxicant in palatogenesis is not well known. Methods In this study, hematoxylin‐eosin and immunofluorescence staining were employed to evaluate the phenotypes and the expression of related markers in the LiCl‐treated mice model. The palatal mesenchymal cells were cultured in vitro, and stimulated with LiCl or SKL2000, and co‐treated with CASIN. β‐catenin protein and other cytoskeleton associated markers were evaluated by Western blotting. Results We found that Lithium disrupted palate elevation by increasing the expression of β‐catenin in C57BL/6J mice with the high incidence of cleft palate (62.5%). LiCl disturbed the F‐actin responsible for cytoskeletal remodeling in mesenchymal cells, which proved to be essential in generating the elevating force during palatal elevation. Additionally, our Western blotting analysis revealed that the overexpression of β‐catenin resulted in up‐regulation of Cdc42, which mediated the downstream F‐actin synthesis. Conclusions We concluded the LiCl‐induced β‐catenin overexpression delayed murine palatal shelf elevation by disturbing Cdc42 mediated F‐actin cytoskeleton synthesis in the palatal mesenchyme.

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Section: Introductionmentioning

confidence: 99%

Lithium‐induced overexpression of β‐catenin delays murine palatal shelf elevation by Cdc‐42 mediated F‐actin remodeling in mesenchymal cells

Wang

Liu

et al. 2020

Birth Defects Research

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“…Recently, several studies have focused on the crosstalk between AhR and other signal pathways [ 32 – 35 ]. It has been reported that TCDD, a high-affinity ligand of AhR, was able to increase the phosphorylation level of AKT and GSK-3 β [ 36 ] and activate β -catenin [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Enhances Melanogenesis via the AhR‐Dependent AKT/GSK‐3β/β‐Catenin Pathway in Normal Human Epidermal Melanocytes

Xie

2020

Evidence-Based Complementary and Alternative Medicine

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Astragalus membranaceus root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS-IV), a main active extract of the Astragalus membranaceus root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS-IV stimulated melanin synthesis and upregulated the expression of melanogenesis-related genes in a concentration-dependent manner in NHEMs. AS-IV could activate the aryl hydrocarbon receptor (AhR), and AS-IV-induced melanogenesis was inhibited in si-AhR-transfected NHEMs. In addition, we showed that AS-IV enhanced the phosphorylation of AKT and GSK-3β and nuclear translocation of β-catenin. AS-IV-induced MITF expression upregulation and melanin synthesis were decreased in the presence of β-catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT/GSK-3β/β-catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS-IV-exposed NHEMs. Our findings show that AS-IV induces melanogenesis through AhR-dependent AKT/GSK-3β/β-catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders.

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“…TGF-β1 has extensive biological functions, including regulating cell growth, differentiation, migration, matrix formation, and damage repair [24][25][26]. It is the most in-depth and most powerful pro brotic cytokine currently studied [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil reduces epidural fibrosis by regulating TGF-β1/Smad2/3 axis to repress the proliferation, migration and differentiation of fibroblasts

Zhu¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background Excessive fibroblasts proliferation is believed as a major reason in the process of epidural fibrosis, which is known as a troublesome complication of lumbar laminectomy clinically. Mycophenolate mofetil (MMF) is a kind of immunosuppressant, previous studies had shown that it has the function of preventing fibrosis, but the role and mechanism are still unclear. In this study, we determined the repressed effect of MMF on fibroblasts proliferation, migration and differentiation in surgical-induced epidural fibrosis and the underlying mechanism. Methods In vitro, the impacts of MMF on cell viability were measured by cell counting kit-8 (CCK-8) assay and the fibroblasts proliferation rates were determined by using EdU incorporation, cell cycle assays and western blot. Additionally, the impacts of MMF on fibroblasts migration and differentiation were analyzed by cell wound scratch assay, transwell assay, immunofluorescence analysis and western blot. In vivo, we built epidural fibrosis models in rats and locally applied MMF. Histological and immunohistochemical staining were used to determine the effect of MMF on reducing epidural fibrosis and fibroblasts functions. Results CCK-8 assay demonstrated that MMF repressed fibroblasts proliferation in a time- and a dose-dependent manner. EdU incorporation assay and cell cycle analysis proved the inhibition effect of MMF on the proliferation of fibroblasts. Cell wound scratch assay, transwell assay and immunofluorescence proved the inhibition effect of MMF on the migration and differentiation of fibroblasts. Western blotting analysis proved that MMF inhibited the expression of TGF-β1, p-Smad2 and p-Smad3. The expression of proliferation proteins, migration proteins and differentiation proteins were downregulated. In addition, histological and immunohistochemical stain showed that MMF reduces epidural fibrosis by repressing the proliferation, migration and differentiation of fibroblasts. Conclusion MMF could inhibit the proliferation, migration and differentiation of fibroblasts, it reduced surgical-induced epidural fibrosis as well. TGF-β1/Smad2/3 axis may be the latent mechanism in MMF reduced epidural fibrosis. It might provide a new notion for mitigating surgery-induced epidural fibrosis.

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TCDD inhibited the osteogenic differentiation of human fetal palatal mesenchymal cells through AhR and BMP-2/TGF-β/Smad signaling

Cited by 21 publications

References 51 publications

Lithium‐induced overexpression of β‐catenin delays murine palatal shelf elevation by Cdc‐42 mediated F‐actin remodeling in mesenchymal cells

Lithium‐induced overexpression of β‐catenin delays murine palatal shelf elevation by Cdc‐42 mediated F‐actin remodeling in mesenchymal cells

Astragaloside IV Enhances Melanogenesis via the AhR‐Dependent AKT/GSK‐3β/β‐Catenin Pathway in Normal Human Epidermal Melanocytes

Mycophenolate mofetil reduces epidural fibrosis by regulating TGF-β1/Smad2/3 axis to repress the proliferation, migration and differentiation of fibroblasts

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