Dataset Information

HMGB1 promotes Ox-LDL-induced endothelial cell damage by inhibiting PI3K/Akt signaling pathway.

ABSTRACT:

Background

Atherosclerosis is the pathological basis of cardio-cerebrovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for atherosclerosis. Ox-LDL leads to endothelial cell (EC) damage and dysfunction through various processes and promotes the occurrence and deterioration of atherosclerosis. High mobility group box-1 (HMGB1) is a protein associated with cellular damage. In the present study, the effect of HMGB1 on ox-LDL-induced EC damage was determined and the underlying mechanism explored.

Materials and methods

Human umbilical vein ECs (HUVECs) were exposed to ox-LDL to induce endothelial damage and changes in HMGB1 expression level were detected using western blotting analysis and reverse transcription-quantitative PCR. To observe the effect of HMGB1 on ox-LDL-induced damage, the HMGB1 expression was downregulated with siRNA, and cell viability, cytotoxicity, and apoptosis rate were assessed. HUVECs were pretreated with LY294002, an inhibitor of the PI3K/Akt pathway, to determine whether the effect of HMGB1 on damage is via the PI3K-Akt pathway.

Results

The results showed that ox-LDL can upregulate HMGB1 expression in HUVECs and downregulation of HMGB1 expression can prevent ox-LDL-induced damage in HUVECs. Furthermore, the effect of HMGB1 on ox-LDL-induced damage could be promoted by inhibiting the PI3K/Akt signaling pathway.

Conclusion

The results indicate HMGB1 may be a promising research target to alleviate ox-LDL-induced EC damage.

SUBMITTER: Huo X

PROVIDER: S-EPMC9768960 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

HMGB1 promotes Ox-LDL-induced endothelial cell damage by inhibiting PI3K/Akt signaling pathway.

Huo Xin X Su Boyou B Qin Guoti G Zhao Liming L

BMC cardiovascular disorders 20221221 1

<h4>Background</h4>Atherosclerosis is the pathological basis of cardio-cerebrovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for atherosclerosis. Ox-LDL leads to endothelial cell (EC) damage and dysfunction through various processes and promotes the occurrence and deterioration of atherosclerosis. High mobility group box-1 (HMGB1) is a protein associated with cellular damage. In the present study, the effect of HMGB1 on ox-LDL-induced EC damage was deter ...[more]

PMID: 36544080

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Project description:BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) is a member of the AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis and prognosis. However, the role of VCP in HCC progression is still unclear.MethodsWe examined the expression of VCP in HCC using the RNA sequencing and microarray data from public databases and measured it in clinical samples and cell lines by western blot, and immunohistochemistry (IHC). We also evaluated the correlation between VCP and clinical features. The VCP-interacting proteins were identified by co-immunoprecipitation combined with mass spectrometry (CoIP/MS). The underlying molecular mechanisms were investigated using in vitro and in vivo models of HCC.ResultsWe found that VCP expression is significantly increased in tumor tissues and is associated with advanced TNM stages and poorer prognosis in HCC patients. In vitro analyses revealed that VCP overexpression promoted HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Conversely, VCP knockdown resulted in the reverse phenotypes. In vivo studies indicated that up-regulated VCP expression accelerated tumor growth in a subcutaneous HCC model. The D1 domain of VCP and A box of HMGB1 were identified as the critical regions for their interaction, and D1 area was required for the tumor-promoting effects induced by VCP expression. VCP enhanced the protein stability of HMGB1 by decreasing its degradation via ubiquitin-proteasome process. Inhibition of HMGB1 markedly attenuated VCP-mediated HCC progression and downstream activation of PI3K/AKT/mTOR signals.ConclusionCollectively, these findings demonstrate that VCP is a potential prognostic biomarker in HCC and exhibits oncogenic roles via PI3K/AKT/mTOR pathway activation. HMGB1 played an essential role in VCP-mediated HCC progression, indicating that VCP and HMGB1 are potential therapeutic targets in human HCC.

Project description:BackgroundMandibular distraction osteogenesis (MDO) is a kind of endogenous tissue engineering technology that lengthens the jaw and opens airway so that a patient can breathe safely and comfortably on his or her own. Endothelial progenitor cells (EPCs) are crucial for MDO-related angiogenesis. Moreover, emerging evidence suggests that heat shock protein 20 (Hsp20) modulates angiogenesis under hypoxic conditions. However, the specific role of Hsp20 in EPCs, in the context of MDO, is not yet known. The aim of this study was to explore the expression of Hsp20 during MDO and the effects of Hsp20 on EPCs under hypoxia.MethodsMandibular distraction osteogenesis and mandibular bone defect (MBD) canine model were established. The expression of CD34, CD133, HIF-1α, and Hsp20 in callus was detected by immunofluorescence on day 14 after surgery. Canine bone marrow EPCs were cultured, with or without optimal cobalt chloride (CoCl2) concentration. Hypoxic effects, caused by CoCl2, were evaluated by means of the cell cycle, cell apoptosis, transwell cell migration, and tube formation assays. The Hsp20/KDR/PI3K/Akt expression levels were evaluated via immunofluorescence, RT-qPCR, and western blot. Next, EPCs were incorporated with either Hsp20-overexpression or Hsp20-siRNA lentivirus. The resulting effects were evaluated as described above.ResultsCD34, CD133, HIF-1α, and Hsp20 were displayed more positive in the callus of MDO compared with MBD. In addition, hypoxic conditions, generated by 0.1 mM CoCl2, in canine EPCs, accelerated cell proliferation, migration, tube formation, and Hsp20 expression. Hsp20 overexpression in EPCs significantly stimulated cell proliferation, migration, and tube formation, whereas Hsp20 inhibition produced the opposite effect. Additionally, the molecular mechanism was partly dependent on the KDR/PI3K/Akt pathway.ConclusionIn summary, herein, we present a novel mechanism of Hsp20-mediated regulation of canine EPCs via Akt activation in a hypoxic microenvironment.

Dataset Information

HMGB1 promotes Ox-LDL-induced endothelial cell damage by inhibiting PI3K/Akt signaling pathway.

Background

Materials and methods

Results

Conclusion

Publications

HMGB1 promotes Ox-LDL-induced endothelial cell damage by inhibiting PI3K/Akt signaling pathway.

Similar Datasets

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