CGRP is essential for protection against alveolar epithelial cell necroptosis by activating the AMPK/L‐OPA1 signaling pathway during acute lung injury DOI
Huiling Jiang, Hui‐Hui Yang,

Yu‐Biao Liu

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(2)

Published: Jan. 9, 2024

Abstract Alveolar epithelial cell (AEC) necroptosis is critical to disrupt the alveolar barrier and provoke acute lung injury (ALI). Here, we define calcitonin gene‐related peptide (CGRP), most abundant endogenous neuropeptide in lung, as a novel modulator of AEC lipopolysaccharide (LPS)‐induced ALI. Upon LPS‐induced ALI, overexpression Cgrp significantly mitigates inflammatory response, alleviates tissue damage, decreases necroptosis. Similarly, CGRP alleviated under LPS challenge vitro. Previously, identified that long optic atrophy 1 (L‐OPA1) deficiency mediates mitochondrial fragmentation, leading In this study, discovered positively regulated fusion through stabilizing L‐OPA1. Mechanistically, elucidate activates AMP‐activated protein kinase (AMPK). Furthermore, blockade AMPK compromised protective effect against following challenge. Our study suggests CRGP‐mediated activation AMPK/L‐OPA1 axis may have potent therapeutic benefits for patients with ALI or other diseases

Language: Английский

Cadmium induced time-dependent kidney injury in common carp via mitochondrial pathway: Impaired mitochondrial energy metabolism and mitochondrion-dependent apoptosis DOI
Jiawen Cui, Yuhao Liu, Zhiyu Hao

et al.

Aquatic Toxicology, Journal Year: 2023, Volume and Issue: 261, P. 106570 - 106570

Published: May 17, 2023

Language: Английский

Citations

52
Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS) DOI Creative Commons
Qianrui Huang, Yue Le, Shusheng Li

et al.

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Language: Английский

Citations

25
mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice DOI Creative Commons

Nan‐Shi‐Yu Yang,

Wenjing Zhong,

Han-Xi Sha

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1927 - 1946

Published: Jan. 1, 2024

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane.However, the molecular mechanism which sevoflurane activates remains unclear.The cGAS-STING pathway an evolutionarily conserved inflammatory defense mechanism.The role sevoflurane-induced inflammasome-dependent and underlying mechanisms require further investigation.We found that prolonged anesthesia with triggered characterized vivo.Interestingly, was activated hippocampus mice receiving sevoflurane.While blockade cGAS RU.521 attenuated mice.In vitro, we treatment significantly microglia, while pre-treatment robustly inhibited activation.Mechanistically, mitochondrial fission released DNA (mtDNA) into cytoplasm, could be abolished Mdivi-1.Blocking mtDNA release via mPTP-VDAC channel inhibitor cytosolic escape reduced finally inhibiting activation.Therefore, regulating targeting may provide a novel therapeutic target POCD.

Language: Английский

Citations

23
The role of mitochondrial quality surveillance in skin aging: Focus on mitochondrial dynamics, biogenesis and mitophagy DOI
Chang Zhang, Xingyu Gao,

Minghe Li

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101917 - 101917

Published: March 25, 2023

Language: Английский

Citations

40
EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis DOI Creative Commons
Chen‐Yu Zhang, Wenjing Zhong,

Yu‐Biao Liu

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102765 - 102765

Published: May 28, 2023

Alveolar epithelial cell (AEC) senescence is a key driver of variety chronic lung diseases. It remains challenge how to alleviate AEC and mitigate disease progression. Our study identified critical role epoxyeicosatrienoic acids (EETs), downstream metabolites arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating senescence. In vitro, we found that 14,15-EET content was significantly decreased senescent AECs. Exogenous EETs supplementation, overexpression CYP2J2, or inhibition degrading enzyme soluble epoxide hydrolase (sEH) increase alleviated AECs' Mechanistically, promoted the expression Trim25 ubiquitinate degrade Keap1 Nrf2 enter nucleus exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) Furthermore, D-galactose (D-gal)-induced premature aging mouse model, degradation Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, inhibitor sEH) inhibited protein p16, p21, γH2AX. Meanwhile, TPPU reduced degree age-related pulmonary fibrosis mice. has confirmed are novel anti-senescence substances for AECs, providing new targets treatment

Language: Английский

Citations

40
NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury DOI Open Access
Jie Zhao,

Ning-xin Zhen,

Qichao Zhou

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5125 - 5125

Published: March 7, 2023

Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, mechanisms which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated NETs and underlying mechanism involved acute lung injury (ALI). found higher expression cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) airways, was reduced Deoxyribonuclease I (DNase I) ALI. The administration STING inhibitor H-151 also significantly relieved injury, but failed to affect high isolated murine from bone marrow acquired human inducing HL-60 differentiate. After PMA interventions, exogenous were obtained such extracted neutrophils. Exogenous intervention vitro vivo resulted airway reversed upon degrading with or inhibiting cGAS-STING as well siRNA STING. In conclusion, participates regulating NETs-mediated pulmonary is expected be new therapeutic target for ARDS/ALI.

Language: Английский

Citations

39
TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury DOI Creative Commons
Wenjing Zhong, Jun Zhang, Jia‐Xi Duan

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 6, 2023

Abstract Background Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) pattern recognition broadly monocytes/macrophages. The influence TREM-1 destiny ALI requires further investigation. Methods decoy LR12 was used to evaluate whether activation induced lipopolysaccharide (LPS)-induced mice. Then we an agonist anti-TREM-1 Ab (Mab1187) activate vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 DRP1 or Rapamycin (an mTOR inhibitor) investigate could induce macrophages, and this process. Results We first observed blockade attenuated alveolar (AlvMs) mice LPS-induced ALI. In vitro, macrophages. has been previously linked polarization migration. discovered had unrecognized function modulating TREM-1-mediated mitochondrial fission, mitophagy, necroptosis. Moreover, promoted Ser616 phosphorylation through signaling, which turn caused surplus fission-mediated consequently exacerbating Conclusion study, reported acted as necroptotic stimulus AlvMs, fueling aggravating also provided compelling evidence suggesting mTOR-dependent fission underpinning TREM-1-triggered inflammation. Therefore, regulation by targeting may provide new therapeutic target for future.

Language: Английский

Citations

34
Mitophagy-related regulated cell death: molecular mechanisms and disease implications DOI Creative Commons

Molin Yang,

Xiang Wei, Xin Yi

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 16, 2024

Abstract During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject to stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular quality control homeostasis, with activation involving both ubiquitin-dependent ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected mitophagy. These diverse RCD been shown be by mitophagy implicated pathogenesis a variety diseases, such as tumors, degenerative ischemia‒reperfusion injury (IRI). Importantly, targeting regulate has excellent therapeutic potential preclinical trials, expected an effective strategy treatment related diseases. Here, we present summary role RCD, focus on molecular mechanisms which regulates RCD. We also discuss implications mitophagy-related context various

Language: Английский

Citations

16
Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases DOI Creative Commons

Mengjiao Xu,

Di Zhang, Jun Yan

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

Citations

14
The role of programmed cell death in organ dysfunction induced by opportunistic pathogens DOI Creative Commons
Wang Yangyanqiu, Li Weng, Xunyao Wu

et al.

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: Jan. 24, 2025

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, intestinal systems. It well-established that infections lead to immune dysregulation, which subsequently contributes MODS in sepsis. However, recent evidence suggests sepsis-related opportunistic pathogens can directly induce failure promoting PCD parenchymal cells each affected organ. This study provides an overview damaged induction host pathogens, proposing innovative strategies for preventing

Language: Английский

Citations

2