Alprostadil attenuates LPS-induced cardiomyocyte injury by inhibiting the Wnt5a/JNK/NF-κB pathway

Yu, Tao; Dong, Di; Guan, Jialiang; Sun, Jialin; Guo, Mingzhou; Wang, Q

doi:10.1007/s00059-019-4837-0

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…Very recently, a study indicated that the activation of JNK promoted the activation of NF-κB, further increasing the release of inflammatory factors. 22 Moreover, the JNK inhibitor SP600125 inhibited PM2.5-induced expression of the inflammatory mediator IL-6 in human osteoarthritis synovial fibroblasts. 23 As predicted, in our study, we also found that GSK-3β inhibitors inhibited the ratio of p-JNK/JNK in HBECs caused by PM2.5.…”

Section: Discussionmentioning

confidence: 98%

GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

Zou

Dong

et al. 2021

COPD

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Background and Purpose: PM2.5-associated airway inflammation has recently been recognized as pivotal to the development of COPD. Aberrant glycogen synthase kinase (GSK)-3β signaling is linked to the inflammatory response. Therefore, we investigated the effects of GSK-3β inhibitors on the PM2.5-induced inflammatory response in bronchial epithelial cells. Methods: The production of phosphorylated GSK-3β (p-GSK-3β) was analyzed by immunohistochemistry with PM2.5-induced mice. HBECs were treated with various inhibitors targeting GSK-3β or JNK before PM2.5 stimulation. The production of GSK-3β signaling was analyzed by Western blotting. Inflammatory cytokine production was detected by qRT-PCR and ELISA. Results: PM2.5 exposure caused lung inflammation, upregulated serum concentrations of HMGB1 and IL-6, decreased IL-10 expression, and significantly attenuated p-GSK-3β production in mice. HBECs exposed to PM2.5 showed significantly reduced p-GSK-3β production, an increased ratio of p-JNK/JNK, increased NF-κB activation and IκB degradation, and upregulated the inflammatory cytokines HMGB1 and IL-6. Intervention with GSK-3β inhibitors TDZD-8 and SB216763 significantly suppressed PM2.5-induced outcomes. Moreover, the JNK inhibitor SP600125 also reduced the level of NF-κB phosphorylation induced by PM2.5. The differences in the levels of inflammation-related cytokines in the TDZD-8 groups were greater than those in the SB216763 groups. Conclusion: Inhibition of GSK-3β weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-κB signaling pathway in bronchial epithelial cells.

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Section: Discussionmentioning

confidence: 98%

GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

Zou

Dong

et al. 2021

COPD

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“…ROR1 and FZD5 are receptors for Wnt5a, which have been shown to be upstream in the activation of NF-κB by Wnt5a ( Barbero et al, 2019 ; Chen et al, 2019 ; Tai et al, 2021 ). Moreover, LPS has been reported to activate the Wnt5a/JNK/NF-κB pathway in H9c2 cells ( Yu et al, 2020 ). Pretreatment with the JNK inhibitor SP60025 significantly reduced the levels of NF-κB in the nucleus which were higher than those induced by silenced Wnt5a (siWnt5a), indicating that other signaling pathways are involved in the Wnt5a/NF-κB pathway besides JNK ( Yu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that inhibition of the NF-κB signaling pathway downregulated the overexpression of Wnt5a induced by injury ( Sucre et al, 2020 ). In addition, LPS-induced activation of Wnt5a can indirectly regulate NF-κB expression through JNK signaling ( Yu et al, 2020 ). Zhao et al (2015) proposed that the upregulation of Wnt5a mediated a positive feedback loop in the inflammatory response through the PI3K/AKT/NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Sun

Wang

Liu³

et al. 2022

Front. Chem.

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This study aimed to explore the effects of exosomes derived from human gingival mesenchymal stem cells (GMSC-Exo) on the inflammatory response of periodontal ligament stem cells (PDLSCs) in an inflammatory microenvironment in order to restore the regenerative potential of PDLSCs, which promotes periodontal tissue regeneration in patients with periodontitis. Periodontitis is a chronic infectious disease characterized by periodontal tissue inflammation and alveolar bone destruction. PDLSCs are regarded as promising seed cells for restoring periodontal tissue defects because of their ability to regenerate cementum/PDL-like tissue and alveolar bone. However, PDLSCs in the inflammatory environment show significantly attenuated regenerative potential. GMSC-Exo have been reported to have anti-inflammatory and immunosuppressive properties. In this study, we investigated the effects of GMSC-Exo on the inflammatory response of PDLSCs induced by lipopolysaccharides (LPS). LPS was used to simulate the inflammatory microenvironment of periodontitis in vitro. GMSC-Exo were extracted from the culture supernatant of GMSCs by ultracentrifugation. We found that GMSC-Exo attenuated the inflammatory response of PDLSCs induced by LPS. Furthermore, compared to treatment with LPS, treatment with GMSC-Exo attenuated the expression of NF-κB signaling and Wnt5a in LPS-induced PDLSCs. In conclusion, we confirmed that GMSC-Exo could suppress the inflammatory response of PDLSCs by regulating the expression of NF-κB signaling and Wnt5a, which paves the way for the establishment of a therapeutic approach for periodontitis.

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“…Noncanonical Wnt5a signaling comprises two main pathways: Wnt5a/Ca 2+ pathway and the Wnt5a/JNK or planar cell polarity (PCP) pathway [37]. Therein JNK signaling was widely demonstrated to be involved in in ammation [36,38,39]. Activated JNK participated in stimulation of many in ammatory cytokines by LPS [39,40].…”

Section: Discussionmentioning

confidence: 99%

“…Therein JNK signaling was widely demonstrated to be involved in in ammation [36,38,39]. Activated JNK participated in stimulation of many in ammatory cytokines by LPS [39,40]. Phosphorylation of JNK mediated hepatoxicity in acetaminophen-induced ALF [20].…”

Section: Discussionmentioning

confidence: 99%

Noncanonical Wnt5a/JNK Signaling Contributes to the Development of D-Gal/LPS-Induced Acute Liver Failure

Fan

Sun

et al. 2022

Inflammation

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Acute liver failure (ALF) is a deadly clinical disorder with few effective treatments and unclear pathogenesis. In our previous study, we demonstrated that aberrant Wnt5a expression was involved in acute on chronic liver failure. However, the role of Wnt5a in ALF is unknown. We investigated the expression of Wnt5a and its downstream signaling of c-jun N-terminal kinase (JNK) in a mouse model of ALF established by co-injection of D-galactosamine (D-Gal) and lipopolysaccharide (LPS) in C57BL/6 mice. We also investigated the role of Box5, a Wnt5a antagonist in vivo. Moreover, the effect of Wnt5a/JNK signaling on downstream in ammatory cytokines expression, phagocytosis and migration in THP-1 macrophages was studied in vitro. Aberrant Wnt5a expression and JNK activation were detected in D-Gal/LPS-induced ALF mice. Box5 pretreatment reversed JNK activation, and eventually decreased the mortality rate of D-Gal/LPS-treated mice with reduced hepatic necrosis and apoptosis, serum ALT and AST levels, and liver in ammatory cytokines expression, although the last was not signi cant. We further demonstrated that recombined Wnt5a (rWnt5a) induced tumor necrosis α (TNF-α) and Interleukin-6 (IL-6) mRNA expression, and increased the phagocytosis ability of THP-1 macrophages in a JNK-dependent manner, which could be restored by Box5. In addition, rWnt5a-induced migration of THP-1 macrophages was also turned by Box5. Our ndings suggested that Wnt5a/JNK signaling play important role in the development of ALF, and Box5 could have particular hepatoprotecive effects in ALF.

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Alprostadil attenuates LPS-induced cardiomyocyte injury by inhibiting the Wnt5a/JNK/NF-κB pathway

Cited by 11 publications

References 42 publications

GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

Exosomes Derived From Human Gingival Mesenchymal Stem Cells Attenuate the Inflammatory Response in Periodontal Ligament Stem Cells

Noncanonical Wnt5a/JNK Signaling Contributes to the Development of D-Gal/LPS-Induced Acute Liver Failure

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