Lipopolysaccharide-Induced Acute Lung Injury Is Associated with Increased Ran-Binding Protein in Microtubule-Organizing Center (RanBPM) Molecule Expression and Mitochondria-Mediated Apoptosis Signaling Pathway in a Mouse Model

Lv, Xiaojing; Lu, Xiyi; Zhu, Ji-Xiao; Wang, Qian

doi:10.12659/msm.923172

Cited by 6 publications

(3 citation statements)

References 33 publications

(33 reference statements)

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“…ALI is a life-threatening disorder accompanied by high mortality (32). During the pathological process of ALI, excessive inflammatory response causes damage to organs (33).…”

Section: Discussionmentioning

confidence: 99%

Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway

et al. 2022

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Acute lung injury (ALI) is a common complication in patients with sepsis and is accompanied by high mortality. The present study aimed to investigate if the organic compound citrulline has a protective against lipopolysaccharide (LPS)-stimulated ALI and its potential mechanisms. ALI was induced in mice by intraperitoneal (i.p.) injection of LPS (10 mg/kg). Citrulline (1 g/kg/day) was administrated i.p. 7 days prior to LPS injection. Mouse lung vascular endothelial cells (MLVECs) were divided into five groups: Control, LPS, LPS + Cit, LPS + N-acetyl-L-cysteine (NAC) and LPS + Cit + ML385. Lung injury was determined by morphology changes. Apoptosis and pyroptosis were detected using western blot analysis and immunofluorescence. The present results indicated that citrulline can significantly attenuate ALI. Citrulline pretreatment decreased the expression of NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) inflammasome and decreased pyroptosis and apoptosis. Intervention with the total reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine attenuated NLRP3 inflammasome-associated pyroptosis and apoptosis in LPS-treated MLVECs. Citrulline pretreatment inhibited pyroptotic cell death and apoptosis induced by LPS. Citrulline decreased accumulation of intracellular ROS and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Furthermore, the Nrf2 inhibitor ML385 reversed ROS generation, NLRP3 inflammasome-mediated pyroptosis and apoptosis suppressed by citrulline. In summary, the present data demonstrated that citrulline may confer protection against ALI via inhibition of ROS/NLRP3 inflammasome-dependent pyroptosis and apoptosis via the Nrf2 signaling pathway.

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“…ALI is a life-threatening disorder accompanied by high mortality (32). During the pathological process of ALI, excessive inflammatory response causes damage to organs (33).…”

Section: Discussionmentioning

confidence: 99%

Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway

et al. 2022

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“…Meanwhile, apoptosis of LPStreated PMVECs was reduced after H19 overexpression. Anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax play opposite roles in apoptosis [51]. The increased Bax level and decreased Bcl-2 level in the CLP-operated mice and LPS-treated PMVECs were inverted after H19 overexpression.…”

Section: Discussionmentioning

confidence: 93%

LncRNA H19 alleviates sepsis-induced acute lung injury by regulating the miR-107/TGFBR3 axis

Hao

Wei

2022

BMC Pulm Med

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Objective Acute lung injury (ALI) increases sepsis morbidity and mortality. LncRNA H19 plays a critical role in sepsis. miR-107 is highly-expressed and TGFβ type III receptor (TGFBR3) is poorly-expressed in sepsis, yet their roles in sepsis development require further investigation. This study aimed to investigate the mechanism of H19 in alleviating sepsis-induced ALI through the miR-107/TGFBR3 axis. Methods Mice were intravenously injected with Ad-H19 adenovirus vector or control vector one week before establishing the mouse model of cecal ligation and puncture (CLP). Pulmonary microvascular endothelial cells (PMVECs) were transfected with oe-H19 or oe-NC plasmids and then stimulated by lipopolysaccharide (LPS). Lung injury was assessed via hematoxylin–eosin staining, measurement of wet-to-dry (W/D) ratio, and TUNEL staining. Levels of H19, miR-107, and TGFBR3 were determined by RT-qPCR. Apoptosis of PMVECs was evaluated by flow cytometry. Levels of Bax and Bcl-2 in lung tissues and PMVECs were measured using Western blot. Total protein concentration and the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were quantified. Levels of TNF-α, IL-1β, IL-6, and IL-10 in BALF, lung tissues, and PMVECs were measured by ELISA. Cross-linking relationships among H19, miR-107 and TGFBR3 were verified by dual-luciferase and RIP assays. Results H19 was poorly-expressed in CLP-operated mice. H19 overexpression attenuated sepsis-induced ALI, which was manifested with complete alveolar structure, decreased lung injury score and lung W/D ratio, and inhibited apoptosis in CLP-operated mice, which was manifested with decreased number of TUNEL-positive cells and Bax level and increased Bcl-2 level. CLP-operated mice had increased concentration of total protein and number of total cells, neutrophils, and macrophages in BALF, which was nullified by H19 overexpression. H19 overexpression declined levels of TNF-α, IL-1β, and IL-6 and elevated IL-10 levels. H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. H19 targeted TGFBR3 as the ceRNA of miR-107. miR-107 overexpression or silencing TGFBR3 partially averted the inhibition of H19 overexpression on LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. Conclusion LncRNA H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production and attenuated sepsis-induced ALI by targeting TGFBR3 as the ceRNA of miR-107.

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“…Recently, Li and colleagues found that severe fever with thrombocytopenia syndrome virus (SFTSV) infection triggers BAK upregulation and BAX activation in THP-1 cells, leading to mtDNA oxidization and subsequent cytosolic release ( 64 ). Additionally, ALI models induced by LPS in mice are characterized by an increased expression of BAK and BAX, indicating the participation of MOMP mediated by BAK/BAX in ALI/ARDS ( 65 ).…”

Section: Mechanisms Of Mtdna Release In Ali/ardsmentioning

confidence: 99%

Role of released mitochondrial DNA in acute lung injury

et al. 2022

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Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is a form of acute-onset hypoxemic respiratory failure characterised by an acute, diffuse, inflammatory lung injury, and increased alveolar-capillary permeability, which is caused by a variety of pulmonary or nonpulmonary insults. Recently, aberrant mitochondria and mitochondrial DNA(mtDNA) level are associated with the development of ALI/ARDS, and plasma mtDNA level shows the potential to be a promising biomarker for clinical diagnosis and evaluation of lung injury severity. In mechanism, the mtDNA and its oxidised form, which are released from impaired mitochondria, play a crucial role in the inflammatory response and histopathological changes in the lung. In this review, we discuss mitochondrial outer membrane permeabilisation (MOMP), mitochondrial permeability transition pore(mPTP), extracellular vesicles (EVs), extracellular traps (ETs), and passive release as the principal mechanisms for the release of mitochondrial DNA into the cytoplasm and extracellular compartments respectively. Further, we explain how the released mtDNA and its oxidised form can induce inflammatory cytokine production and aggravate lung injury through the Toll-like receptor 9(TLR9) signalling, cytosolic cGAS-stimulator of interferon genes (STING) signalling (cGAS-STING) pathway, and inflammasomes activation. Additionally, we propose targeting mtDNA-mediated inflammatory pathways as a novel therapeutic approach for treating ALI/ARDS.

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Lipopolysaccharide-Induced Acute Lung Injury Is Associated with Increased Ran-Binding Protein in Microtubule-Organizing Center (RanBPM) Molecule Expression and Mitochondria-Mediated Apoptosis Signaling Pathway in a Mouse Model

Cited by 6 publications

References 33 publications

Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway

Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway

LncRNA H19 alleviates sepsis-induced acute lung injury by regulating the miR-107/TGFBR3 axis

Role of released mitochondrial DNA in acute lung injury

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