scholarly journals Acute Inflammatory Response in Osteoporotic Fracture Healing Augmented with Mechanical Stimulation is Regulated In Vivo through the p38-MAPK Pathway

2021 ◽  
Vol 22 (16) ◽  
pp. 8720
Author(s):  
Simon Kwoon Ho Chow ◽  
Can Cui ◽  
Keith Yu Kin Cheng ◽  
Yu Ning Chim ◽  
Jinyu Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Fracture Healing ◽  
P38 Mapk ◽  
Osteoporotic Fracture ◽  
Mechanical Stimulation ◽  
Mapk Pathway ◽  
Acute Inflammatory Response ◽  
P38 Mapk Pathway ◽  
Response Expression

Low-magnitude high-frequency vibration (LMHFV) has previously been reported to modulate the acute inflammatory response of ovariectomy-induced osteoporotic fracture healing. However, the underlying mechanisms are not clear. In the present study, we investigated the effect of LMHFV on the inflammatory response and the role of the p38 MAPK mechanical signaling pathway in macrophages during the healing process. A closed femoral fracture SD rat model was used. In vivo results showed that LMHFV enhanced activation of the p38 MAPK pathway at the fracture site. The acute inflammatory response, expression of inflammatory cytokines, and callus formation were suppressed in vivo by p38 MAPK inhibition. However, LMHFV did not show direct in vitro enhancement effects on the polarization of RAW264.7 macrophage from the M1 to M2 phenotype, but instead promoted macrophage enlargement and transformation to dendritic monocytes. The present study demonstrated that p38 MAPK modulated the enhancement effects of mechanical stimulation in vivo only. LMHFV may not have exerted its enhancement effects directly on macrophage, but the exact mechanism may have taken a different pathway that requires further investigation in the various subsets of immune cells.

scholarly journals Gold Nanoparticles Combined Human β-Defensin 3 Gene-Modified Human Periodontal Ligament Cells Alleviate Periodontal Destruction via the p38 MAPK Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Lingjun Li ◽  
Yangheng Zhang ◽  
Min Wang ◽  
Jing Zhou ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Osteogenic Differentiation ◽  
P38 Mapk ◽  
Periodontal Ligament ◽  
Mapk Pathway ◽  
Periodontal Regeneration ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
P38 Mapk Pathway

Periodontitis is a chronic inflammatory disease with plaques as the initiating factor, which will induce the destruction of periodontal tissues. Numerous studies focused on how to obtain periodontal tissue regeneration in inflammatory environments. Previous studies have reported adenovirus-mediated human β-defensin 3 (hBD3) gene transfer could potentially enhance the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and bone repair in periodontitis. Gold nanoparticles (AuNPs), the ideal inorganic nanomaterials in biomedicine applications, were proved to have synergetic effects with gene transfection. To further observe the potential promoting effects, AuNPs were added to the transfected cells. The results showed the positive effects of osteogenic differentiation while applying AuNPs into hPDLCs transfected by adenovirus encoding hBD3 gene. In vivo, after rat periodontal ligament cell (rPDLC) transplantation into SD rats with periodontitis, AuNPs combined hBD3 gene modification could also promote periodontal regeneration. The p38 mitogen-activated protein kinase (MAPK) pathway was demonstrated to potentially regulate both the in vitro and in vivo processes. In conclusion, AuNPs can promote the osteogenic differentiation of hBD3 gene-modified hPDLCs and periodontal regeneration via the p38 MAPK pathway.

Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation: In vivo and in vitro verification

2020 ◽  
Vol 249 ◽  
pp. 112390 ◽  
Author(s):  
Xihai Li ◽  
Zhenli Zhang ◽  
Wenna Liang ◽  
Jianwei Zeng ◽  
Xiang Shao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
P38 Mapk Pathway

scholarly journals B7-H1(PD-L1) confers chemoresistance through ERK and p38 MAPK pathway in tumor cells

2018 ◽  
Author(s):  
Xiaosheng Wu ◽  
Yanli Li ◽  
Xin Liu ◽  
Siyu Cao ◽  
Susan M. Harrington ◽  
...  
Keyword(s):  
Tumor Cells ◽  
P38 Mapk ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Dependent Manner ◽  
Intracellular Signaling Pathway ◽  
Development Of Resistance ◽  
P38 Mapk Pathway

ABSTRACTDevelopment of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of patients with cancer. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance remains underestimated. It has been recently observed that overexpression of B7-H1(PD-L1) confers chemoresistance in human cancers, however the underlying mechanisms are unclear. Here we show that the development of chemoresistance depends on the increased activation of ERK pathway in tumor cells overexpressing B7-H1. Conversely, B7-H1 deficiency renders tumor cells susceptible to chemotherapy in a cell-context dependent manner through activation of the p38 MAPK pathway. B7-H1 in tumor cells associates with the catalytic subunit of a DNA-dependent serine / threonine protein kinase (DNA-PKcs). DNA-PKcs is required for the activation of ERK or p38 MAPK in tumors expressing B7-H1, but not in B7-H1 negative or B7-H1 deficient tumors. Ligation of B7-H1 by anti-B7-H1 monoclonal antibody (H1A) increased the sensitivity of human triple negative breast tumor cells to cisplatin therapy in vivo. Our results suggest that B7-H1(PD-L1) expression in cancer cells modifies their chemosensitivity towards certain drugs and targeting B7-H1 intracellular signaling pathway is a new way to overcome cancer chemoresistance.

Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway

2007 ◽  
Vol 86 (6) ◽  
pp. 331-344 ◽  
Author(s):  
Haitao Wu ◽  
Xuan Wang ◽  
Shuhong Liu ◽  
Yan Wu ◽  
Tong Zhao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Myogenic Differentiation ◽  
P38 Mapk Pathway

scholarly journals FR167653 inhibits fibronectin expression and apoptosis in diabetic glomeruli and in high-glucose-stimulated mesangial cells

2008 ◽  
Vol 295 (2) ◽  
pp. F595-F604 ◽  
Author(s):  
Dong-Sub Jung ◽  
Jin Ji Li ◽  
Seung-Jae Kwak ◽  
Sun Ha Lee ◽  
Jehyun Park ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Expression ◽  
P38 Mapk ◽  
High Glucose ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Fibronectin Expression

Previous in vitro studies suggest that the p38 MAPK pathway may be involved in the pathogenesis of diabetic nephropathy, but the consequences of the inhibition of the p38 MAPK pathway have not been well elucidated in diabetic (DM) glomeruli. This study was undertaken to investigate the effect of p38 MAPK inhibitor, FR167653, on fibronectin expression and apoptosis in DM glomeruli and in high-glucose-stimulated mesangial cells (MC). In vivo, 32 Sprague-Dawley rats were injected with diluent (control, N = 16) or streptozotocin intraperitoneally (DM, N = 16). Eight rats from each group were treated with FR167653 for 3 mo. In vitro, rat MC were exposed to medium containing 5.6 mM glucose or 30 mM glucose [high glucose (HG)] with or without 10−6 M FR167653 for 24 h. Fibronectin mRNA and protein expression were determined by real-time PCR and Western blot, respectively. Western blot for apoptosis-related molecules, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, and Hoechst 33342 staining were performed to determine apoptosis. FR167653 ameliorated the increases in fibronectin-to-GAPDH mRNA ratio and protein expression in DM glomeruli by 89 and 79% and in HG-stimulated MC by 70 and 91%, respectively ( P < 0.05). Under diabetic conditions, Bcl-2 protein expression was decreased, whereas cleaved caspase-3 protein expression was increased ( P < 0.05), and these changes were inhibited by FR167653 treatment. Apoptotic cells were also significantly increased in DM glomeruli and in HG-stimulated MC ( P < 0.05), and FR167653 ameliorated these increases in apoptotic cells, both in vivo and in vitro. In conclusion, these findings suggest that the inhibition of the p38 MAPK pathway has a beneficial effect on the development of diabetic nephropathy by inhibiting the increase in fibronectin expression and apoptosis.

scholarly journals Complement C3a Activates Astrocytes to Promote Medulloblastoma Progression through TNF -α

2021 ◽  
Author(s):  
Biao Gong ◽  
Duancheng Guo ◽  
Chaonan Zheng ◽  
Zhen Ma ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Receptor Antagonist ◽  
P38 Mapk ◽  
Western Blotting ◽  
Mapk Pathway ◽  
Receptor Expression ◽  
Immunofluorescent Staining ◽  
P38 Mapk Pathway ◽  
Tnf Α

Abstract Background: Medulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is therefore critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms for how astrocytes are regulated and activated to promote MB remain elusive. Methods: By taking advantage of Math1-Cre/Ptch1 loxp/loxp mice which spontaneously develop MB, primary MB cells and astrocytes were isolated then underwent administration and coculture in vitro . Immunohistochemistry was utilized to determine C3a presence in MB sections. MB cell proliferation was evaluated by immunofluorescent staing. GFAP and cytokines expression in C3a stimulated astrocytes was assessed by immunofluorescent staining, western blotting, q-PCR and ELISA method. C3a receptor and TNF-α receptor expression was determined by PCR. p38 MAPK pathway was detected by western blotting. Transplanted MB mice were treated with C3a receptor or TNF-α receptor antagonist to investigate their role in MB progression in vivo . Results: We found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via p38 MAPK pathway. Moreover, we discovered that C3a upregulated production of pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with TNF-α receptor antagonist, indicating a TNF-α -dependent event. Indeed, we further demonstrated that administration of selective C3a receptor or TNF-α receptor antagonist to subcutaneous transplantation MB mice suppressed tumor progression in vivo . Conclusions: C3a was released during MB development. C3a triggered astrocytes activation and TNF-α production via p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. The findings imply that targeting to C3a and TNF-α may represent a potential novel therapeutic approach for human MB.

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