High Glucose Suppresses Keratinocyte Migration Through the Inhibition of p38 MAPK/Autophagy Pathway

Li, Lingfei; Zhang, Junhui; Zhang, Qiong; Zhang, Dongxia; Fei, Xiang; Jia, Jiezhi; Wei, Ping; Zhang, Jiaping; Hu, Jiongyu; Huang, Yuesheng

doi:10.3389/fphys.2019.00024

Cited by 61 publications

(66 citation statements)

References 39 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, infection and other factors can also induce p38 MAPK activation. 48 In the present study, consistent results were achieved with TG induction in H9c2 cells, and high expression of p-p38 MAPK was found.…”

Section: Discussionsupporting

confidence: 90%

Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress

Zhu

Ling

Zhou

et al. 2020

DDDT

View full text Add to dashboard Cite

Background: Myocardial ischaemia-reperfusion injury (IRI) has been confirmed to induce endoplasmic reticulum stress (ERS) when myocardial cell function continues to deteriorate to a certain degree. The clinical applications of effective tested strategies are sometimes inconsistent with the applications evaluated in experiments, although reasonable mechanisms and diverse signalling pathways have been broadly explored. Dexmedetomidine (DEX) has been shown to attenuate IRI of the heart in animal studies. This study aimed to determine whether DEX can protect injured cardiomyocytes under hypoxia/reoxygenation (H/R) at the cellular level and whether the mechanism is related to ERS and the p38 MAPK pathway. Methods: H9c2 cells were subjected to H/R or thapsigargin (TG) to build a model. DEX or 4-PBA was added to the medium either 1 h or 24 h before modelling, respectively. Model parameters were determined by assessing cell viability and injury, which were measured by assessing cell counting kit-8 (CCK8), lactate dehydrogenase (LDH) release and flow cytometry results, and the expression of GRP78, CHOP and caspase-12. In addition, the protein expression of p38MAPK and p-p38MAPK was examined, and SB202190, a negative regulator, was also preincubated in medium. Results: Compared to that of cells in the control group, the activity of cells in the H/R and TG groups was decreased dramatically, and the LDH concentration and proportion of apoptotic cells were increased. DEX could correspondingly reverse the changes induced by H/R or TG. Additionally, DEX effectively attenuated ERS defined as increased expression of GRP78, CHOP and caspase-12. Additionally, DEX could obviously depress the P38 MAPK phosphorylation and high p-p38 MAPK expression in the TG group, indicating DEX has a function similar to that of SB202190. Conclusion: H/R injury in H9c2 cells can lead to abnormal ERS and apoptosis, as well as activation of the p38MAPK signalling pathway. DEX can protect cardiomyocytes by intervening in ERS, regulating p38MAPK and the downstream apoptotic signalling pathway.

show abstract

Section: Discussionsupporting

confidence: 90%

Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress

Zhu

Ling

Zhou

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…In fact, the crosstalk between MAPK and autophagy has been elucidated enormously in different cell types. 16,17 In addition, our previous study also suggests that the MAPK signaling pathway is activated on MNT surface in osteoblasts. 18 Taken together, we hypothesize that the MNT surface may induce autophagy response through MAPK pathway and consequently influence the macrophages M2 polarization.…”

Section: Introductionmentioning

confidence: 89%

The Role of Autophagy in M2 Polarization of Macrophages Induced by Micro/Nano Topography

Luo

Meng

et al. 2020

IJN

View full text Add to dashboard Cite

Background: The proper topography of implant surface can induce macrophages polarization, whereas the regulation mechanism has not been fully deciphered. The study aimed to examine the regulation mechanism of macrophages M2 polarization by titanium (Ti) implant surface micro/nano topography. Results: Firstly, the titanium implant micropits-nanotubular surface with ~30 nm diameters (MNT) can induce the M2 polarization of RAW264.7 spontaneously, as indicated by the spindle-like cell morphological alteration and specific molecular marker arginase-1 (Arg1) expression. Next, the autophagic vacuoles (AVs) number is significantly increased on MNT surface, as confirmed by the monodansylcadaverine (MDC) and CYTO-ID staining as well as the transmission electron microscope (TEM) observation. In addition, increasing or decreasing the autophagosomes number by rapamycin or 3-methyladenine (3-MA) will result in augmentation or attenuation of Arg1. Furthermore, blocking the fusion between autophagosomes and lysosomes by bafilomycin also significantly reduces Arg1, even in the presence of rapamycin. Finally, the ERK phosphorylation is selectively upregulated on MNT surface and the AVs number and Arg1 expression are significantly suppressed by U0126 treatment. Conclusion: Our findings suggest that the ERK-Beclin-1-autophagy axis may play a pivotal role in the regulation of M2 polarization induced by nanotopography.

show abstract

“…Previous study has confirmed the expressions of LC3B and Beclin1 were significantly upregulated in rat bone marrow mesenchymal stem cells, which were stimulated in high glucose (HG) condition, with increased formation of autophagosomes . However, the dysfunction of autophagosomes was found in skin epithelium of diabetic mice, accompanied with the decrease of LC3II/I expression ratio . The imbalance of autophagy seems to be able to explain the abnormal expression of inflammatory cytokines in cells stimulated by HG.…”

Section: Introductionmentioning

confidence: 91%

High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C

Huang

Kuang

Shen

et al. 2019

Journal of Periodontology

View full text Add to dashboard Cite

Background: Hyperglycemic micro-environment induced by diabetes could regulate the response of periodontal tissues to pathogenic microorganisms in which disruption of autophagy lysosomal pathway (ALP) may participate. This study aimed to explore the mechanisms underlying how high glucose (HG) regulates ALP in gingival epithelial cells (GECs). Methods:Human gingival tissues in healthy group (C), periodontitis group (P), diabetes group (DM), and diabetes + periodontitis group (DP) were collected and were applied to observe the fusion of autophagy and lysosome. Diabetic mouse model with periodontitis was established and RNA-seq was applied to investigate the expression of ALP-associated genes in gingival epithelium. To explore the key role of ATPase transmembrane v0 domain, subunit c (ATP6V0C) in the disruption of ALP by HG, human gingival epithelial cells (HGECs) were cultured in 5.5 mM/25 mM glucose medium for 48 hours and followed by Porphyromonas gingivalis stimulation for 0, 6, and 12 hours. HBLV-h-ATP6V0C was transfected in HGECs that were stimulated by 25 mM HG condition. Results: Immunofluorescence double staining exhibited the disruption of ALP in human gingival epithelium in diabetes groups and HGECs under 25 mM glucose condition, accompanied with significantly downregulated lysosomal acidity. RNA-seq of mouse gingival epithelium screened out Atp6v0c. Compared with HGECs in normal culture medium, ATP6V0C expression and LC3-II/I expression ratio were significantly downregulated, with an upregulated expression of P62, IL-1 in HGECs under HG condition. Over-expression of ATP6V0C rescued HG-induced disruption of ALP in HBLV-h-ATP6V0C transfected HGECs, with significantly upregulation of LC3-II/I and downregulation of P62, IL-1 . Conclusion: ATP6V0C mediates HG-induced ALP disruption in HGECs, eventually exacerbates periodontal inflammation. K E Y W O R D S chronic periodontitis, human ATP6V0C protein, innate immunity, mouse Atp6v0c protein, type 2 diabetes mellitus J Periodontol. 2020;91:705-714. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article.How to cite this article: Huang X, Kuang S, Shen Z, Liang M, Lin Z. High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C. J Periodontol. 2020;91:705-714. https://

show abstract

High Glucose Suppresses Keratinocyte Migration Through the Inhibition of p38 MAPK/Autophagy Pathway

Cited by 61 publications

References 39 publications

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

<p>The Role of Autophagy in M2 Polarization of Macrophages Induced by Micro/Nano Topography</p>

High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C

Contact Info

Product

Resources

About