SRPK1 promotes sepsis-induced acute lung injury via regulating PI3K/AKT/FOXO3 signaling

Guo, Wei; Hu, Zhansheng

doi:10.1080/08923973.2022.2134789

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…4 ). At the same time, PI3K/AKT pathway was reported to involve in the process of AFC of ALI models [ 15 , 35 – 37 ]. For instance, activation of PI3K signaling was reported to increase AFC associated with ENaC activity in a rat model [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway

Shi,

Huang,

et al. 2024

Cell. Mol. Life Sci.

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Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase β1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

“…Which signaling might mediate PEBP4-modulated ALI and AFC? PI3K/AKT signaling is known as an important pathway in the occurrence and development of ALI [15,[35][36][37]. Coincidentally, a few studies have demonstrated PEBP4 has a tightly connection with PI3K/AKT pathway.…”

Section: Pi3k/akt Signaling Activators Specifically Reverse the Impac...mentioning

confidence: 99%

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway

Shi,

Huang,

et al. 2024

Cell. Mol. Life Sci.

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“…SRPK1 overexpression can promote cell proliferation, inhibit apoptosis in primary human pulmonary microvascular endothelial cells, and alleviate sepsis-induced ALI in vivo through forkhead box O 3-mediated transcriptional inactivation of NLRP3 and inhibition of NLRP3 mRNA and protein expression. However, SRPK1 levels are decreased in patients with sepsis-induced ALI [ 132 ]. Exogenous administration of growth arrest-specific 6 can inhibit TNF-α release and apoptosis and attenuate the activation of NF-κB and MAPK through the Axl/PI3K/Akt pathway [ 133 ].…”

Section: Reviewmentioning

confidence: 99%

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets

Wu,

Mi,

Liu

et al. 2024

Burns &Amp; Trauma

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Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

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Novel Therapeutic Target for ALI/ARDS: Forkhead Box Transcription Factors

Zhu,

Meng,

et al. 2024

Lung

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SRPK1 promotes sepsis-induced acute lung injury via regulating PI3K/AKT/FOXO3 signaling

Cited by 5 publications

References 35 publications

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets

Novel Therapeutic Target for ALI/ARDS: Forkhead Box Transcription Factors

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