HMGB1 in inflammation and cancer

Wang, Shumin; Zhang, Yi

doi:10.1186/s13045-020-00950-x

Cited by 157 publications

(116 citation statements)

References 17 publications

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“…Tissue injury and organ dysfunction, which can further induce different kinds of diseases and infection, occur as a result of excessive amounts of extracellular HMGB1 [13,14]. Recent reports have indicated the crucial role of HMGB1 in inflammatory disorders [13,[15][16][17]; therefore, antagonists that targeted extracellular HMGB1 have become an ideal therapy for the treatment of inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes

Lan

2021

J Orthop Surg Res

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Background Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment. Materials and methods The chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits. Results After chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress. Conclusion In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.

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Section: Introductionmentioning

confidence: 99%

Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes

Lan

2021

J Orthop Surg Res

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“…High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein that is passively released by dead cells or actively secreted into the extracellular environment by inflammatory cells under conditions of cellular stress to regulate innate and adaptive immunity (18). The known HMGB1 receptors include receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR) 2 and TLR4 (19).…”

Section: Introductionmentioning

confidence: 99%

Remote ischemic post‑conditioning alleviates ischemia/reperfusion‑induced intestinal injury via the ERK signaling pathway‑mediated RAGE/HMGB axis

et al. 2021

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Intestinal ischemia reperfusion (I/R) injury is a tissue and organ injury that frequently occurs during surgery and significantly contributes to the pathological processes of severe infection, injury, shock, cardiopulmonary insufficiency and other diseases. However, the mechanism of intestinal I/R injury remains to be elucidated. A mouse model of intestinal I/R injury was successfully established and the model mice were treated with remote ischemic post-conditioning (RIPOC) and/or an ERK inhibitor (CC-90003), respectively. Histopathological changes of the intestinal mucosa were determined by hematoxylin and eosin staining. In addition, the levels of high-mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) expression were confirmed by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry assays. The levels of antioxidants, oxidative stress markers (8-OHdG) and interleukin 1 family members were evaluated by ELISA assays and the levels of NF-κB pathway proteins were analyzed by western blotting. The data demonstrated that RIPOC could attenuate the histopathological features of intestinal mucosa in the intestinal I/R-injury mouse models via the ERK pathway. It was also revealed that HMGB1 and RAGE expression in the mouse models could be markedly reduced by RIPOC (P<0.05) and that these reductions were associated with inhibition of the ERK pathway. Furthermore, it was demonstrated that RIPOC produced significant antioxidant and anti-inflammatory effects following an intestinal I/R injury and that these effects were mediated via the ERK pathway (P<0.05). In addition, RIPOC was demonstrated to suppress the NF-κB (p65)/NLR family pyrin domain containing 3 (NLRP3) inflammatory pathways in the intestinal I/R injury mouse models via the ERK pathway. The findings of the present study demonstrated that RIPOC helped to protect mice with an intestinal I/R injury by downregulating the ERK pathway.

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“…Intranuclear HMGB1 mainly functions as DNA chaperone and can also be released into cytoplasm or extracellular context in response to diverse stimulus (eg, chemoradiotherapy and metabolic stress). Whether extracellular or intracellular HMGB1 has been proved to function as a crucial regulator of autophagy [36][37][38][39]. Here our study focused on intracellular HMGB1.…”

Section: Discussionmentioning

confidence: 99%

HN1 Promotes Proliferation, Metastasis and Attenuates the Chemosensitivity of HCC Cells to Oxaliplatin by Inhibiting Degradation of HMGB1 Through Interacting With TRIM28

Wang

Yao

et al. 2021

Preprint

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Background: The oxaliplatin-based chemotherapy has revealed an encouraging therapeutic efficacy for advanced hepatocellular carcinoma patients. However, the development of resistance limits its clinical utilization. In addition, the chemotherapy resistance in HCC is usually accompanied with other malignant phenotypes, such as cell proliferation and metastasis, which together result in poor prognosis of HCC patients. Therefore, efforts should be made to explore potential regulators which fuel multiple events of HCC progression.Methods: The qRT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to measure mRNA and protein expression. MTT assay, colony formation and Transwell assay were performed to evaluate cell proliferation and metastasis. Flow cytometry was performed to test cell apoptosis. Alkaline Comet assay was performed to measure DNA lesions. Transmission electron microscope analysis provided potent testimony of autophagy. The role of HN1 on the malignant phenotypes of hepatoma carcinoma was demonstrated in vitro and in vivo.Results: The immunohistochemistry analysis of HCC patient tissues revealed that the expression of HN1 was higher in HCC tissues compared to adjacent tissues and was associated with worse prognosis. In vitro, HN1 knockdown inhibited proliferation and metastasis of HCC cells, whereas HN1 overexpression promoted their proliferation and metastasis. In addition, we found that HN1 knockdown sensitized HCC cells to oxaliplatin, which is companied with deteriorated DNA damage and increased cell apoptosis in oxaliplatin-treated HCC cells. In vivo, HN1 knockdown inhibited the tumor growth and metastasis, and promoted the anti-cancer efficiency of oxaliplatin. Mechanically, HN1 prevented HMGB1 from ubiquitination and degradation via autophagy-lysosome pathway, which is related to its interaction with TRIM28, and overexpression of HMGB1 can restore the malignant phenotypes of HN1 knockdown in HCC cells. Furthermore, we found that HN1 can regulate cellular autophagy via HMGB1, which is important to tumor-promoting effect of HN1.Conclusions: In conclusion, we systemically revealed the multiple functions of HN1 in HCC progression and the underlying molecular mechanism, which indicated that HN1 could be a promising therapeutic target for HCC treatment.

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HMGB1 in inflammation and cancer

Cited by 157 publications

References 17 publications

Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes

Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes

Remote ischemic post‑conditioning alleviates ischemia/reperfusion‑induced intestinal injury via the ERK signaling pathway‑mediated RAGE/HMGB axis

HN1 Promotes Proliferation, Metastasis and Attenuates the Chemosensitivity of HCC Cells to Oxaliplatin by Inhibiting Degradation of HMGB1 Through Interacting With TRIM28

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