Genetic determinants of ammonia-induced acute lung injury in mice

Bein, Kiflai; Ganguly, Koustav; Martin, Timothy M.; Concel, Vincent J.; Brant, Kelly A.; Di, Y. Peter; Upadhyay, Swapna; Fabisiak, James P.; Vuga, Louis J.; Kaminski, Naftali; Kostem, Emrah; Eskin, Eleazar; Prows, Daniel R.; Jang, Ann-Soo; Leikauf, George D.

doi:10.1152/ajplung.00276.2020

Cited by 7 publications

(6 citation statements)

References 142 publications

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“…Homology analyses of important differentially expressed lncRNAs have been performed to find out regions of local similarity between rat and human sequences. Some identified homologous sequences have been demonstrated in participating lung injury according to previous studies [ 16 – 25 ]. SNX19 had suggestive single-nucleotide polymorphism association with ammonia-induced acute lung injury and had pathophysiological roles that could be associated with acute lung injury in different ways [ 16 ].…”

Section: Discussionmentioning

confidence: 78%

“…Literature research has found that transcripts of homologous sequences SNX19 (corresponding with lncRNA TCONS_00009865 in rats), KCNQ1OT1 (corresponding with lncRNA TCONS_00030049 in rats), RAB1A (corresponding with lncRNA TCONS_00081686 in rats), CREB1 (corresponding with lncRNA TCONS_00091647 in rats), ABL1 (corresponding with lncRNA TCONS_00175309 in rats), RPS6 (corresponding with lncRNA TCONS_00175309 in rats), NEDD4 (corresponding with lncRNA TCONS_00255085 in rats), and FBXL2 (corresponding with lncRNA TCONS_00277162 in rats) participate in important processes of lung injury [ 16 – 25 ]. These lncRNAs and their homologous sequences may play an important role in intrauterine infection/inflammation-induced lung injury.…”

Section: Resultsmentioning

confidence: 99%

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Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study

et al. 2023

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Background Intrauterine infection/inflammation can result in fetal and neonatal lung injury. However, the biological mechanisms of intrauterine infection/inflammation on fetal and neonatal lung injury and development are poorly known. To date, there are no reliable biomarkers for improving intrauterine infection/inflammation-induced lung injury. Methods An animal model of intrauterine infection/inflammation-induced lung injury was established with pregnant Sprague–Dawley rats inoculated with Escherichia coli suspension. The intrauterine inflammatory status was assessed through the histological examination of the placenta and uterus. A serial of histological examinations of the fetal and neonatal rats lung tissues were performed. The fetal and neonatal rat lung tissues were harvested for next generation sequencing at embryonic day 17 and postnatal day 3, respectively. Differentially expressed mRNAs and lncRNAs were identified by conducting high-throughput sequencing technique. The target genes of identified differentially expressed lncRNAs were analyzed. Homology analyses for important differentially expressed lncRNAs were performed. Results The histopathological results showed inflammatory infiltration, impaired alveolar vesicular structure, less alveolar numbers, and thickened alveolar septa in fetal and neonatal rat lung tissues. Transmission electron micrographs revealed inflammatory cellular swelling associated with diffuse alveolar damage and less surfactant-storing lamellar bodies in alveolar epithelial type II cells. As compared with the control group, there were 432 differentially expressed lncRNAs at embryonic day 17 and 125 differentially expressed lncRNAs at postnatal day 3 in the intrauterine infection group. The distribution, expression level, and function of these lncRNAs were shown in the rat genome. LncRNA TCONS_00009865, lncRNA TCONS_00030049, lncRNA TCONS_00081686, lncRNA TCONS_00091647, lncRNA TCONS_00175309, lncRNA TCONS_00255085, lncRNA TCONS_00277162, and lncRNA TCONS_00157962 may play an important role in intrauterine infection/inflammation-induced lung injury. Fifty homologous sequences in Homo sapiens were also identified. Conclusions This study provides genome-wide identification of novel lncRNAs which may serve as potential diagnostic biomarkers and therapeutic targets for intrauterine infection/inflammation-induced lung injury.

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Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study

et al. 2023

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“…AATF has also been reported overexpressed in various cancerous tissues, including lung and colorectal cancer, as well as lymphomas [ 32 ]. A recent study revealed AATF as one of the candidate genes associated with acute lung injury [ 33 ]. It has been reported that AATF expression increases during disease progression and is involved in a pathway related to airway inflammation in COPD [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease

Qiao

Luo

et al. 2022

Biomolecules

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Frequent acute exacerbations are the leading cause of high rates of hospitalization and mortality in chronic obstructive pulmonary disease (COPD). Despite the enormous worldwide medical burden, reliable molecular markers for effective early diagnosis and prognosis of acute exacerbations are still lacking. Both the host genetics and airway microbiome are known to play potential roles in the pathogenesis of frequent exacerbations. Here, we performed whole exome sequencing (WES) and 16S rRNA gene sequencing to explore the interaction between these two factors and their implications in the pathogenesis of frequent exacerbations. We collected peripheral blood (n = 82), sputum samples (n = 59) and clinical data from 50 frequent-exacerbation phenotype (FE) COPD patients and 32 infrequent-exacerbation phenotype (IE) as controls. Based on filtering the deleterious sites, candidate mutated genes shared only in FE patients and did not occur in the IE group were identified. Microbiota analysis revealed significant differences in bacterial diversity and composition between FE and IE groups. We report the underlying pathogenic gene including, AATF, HTT, CEP350, ADAMTS9, TLL2 genes, etc., and explore their possible genotypic-phenotypic correlations with microbiota dysbiosis. Importantly, we observed that AATF gene mutations were significantly negatively correlated with microbial richness and diversity. Our study indicated several deleterious mutations in candidate genes that might be associated with microbial dysbiosis and the increased risk of frequent acute exacerbations in COPD patients. These results provide novel evidence that exomes and related microbiomes may potentially serve as biomarkers for predicting frequent acute exacerbations in COPD patients.

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“…SNX19 is essential for the lipid raft residence of D 1 R, cAMP production, and promotion of effective D 1 R signaling [20]. SNX19 also regulates the signaling of histamine receptor H4 (HRH4), a GPCR that is important in the initiation and maintenance of inflammation in mouse lung, following ammonia exposure [38].…”

Section: Snx-pxa-rgs-pxc Subfamily In Receptor Signalingmentioning

confidence: 99%

“…There is a dynamic coordinated interaction among the recycling, retrograde, and degradative pathways, which maintains normal cellular functions [2,3]. However, if the SNX-PXA-RGS-PXC subfamily, like all other SNX subfamilies, is dysfunctional and disabled to transport receptor cargoes to their appropriate cellular destinations, there will be the impairment of the above-mentioned pathways, which will negatively affect cellular functions, causing disorders, such as those listed in Table 4 [17][18][19][20]23,27,33,38,[89][90][91][92][93][94][95][96][97][98].…”

Section: Snx-pxa-rgs-pxc Subfamily In Physiology and Pathophysiologymentioning

confidence: 99%

SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking

Amatya

Lee

Asico

et al. 2021

IJMS

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The SNX-PXA-RGS-PXC subfamily of sorting nexins (SNXs) belongs to the superfamily of SNX proteins. SNXs are characterized by the presence of a common phox-homology (PX) domain, along with other functional domains that play versatile roles in cellular signaling and membrane trafficking. In addition to the PX domain, the SNX-PXA-RGS-PXC subfamily, except for SNX19, contains a unique RGS (regulators of G protein signaling) domain that serves as GTPase activating proteins (GAPs), which accelerates GTP hydrolysis on the G protein α subunit, resulting in termination of G protein-coupled receptor (GPCR) signaling. Moreover, the PX domain selectively interacts with phosphatidylinositol-3-phosphate and other phosphoinositides found in endosomal membranes, while also associating with various intracellular proteins. Although SNX19 lacks an RGS domain, all members of the SNX-PXA-RGS-PXC subfamily serve as dual regulators of receptor cargo signaling and endosomal trafficking. This review discusses the known and proposed functions of the SNX-PXA-RGS-PXC subfamily and how it participates in receptor signaling (both GPCR and non-GPCR) and endosomal-based membrane trafficking. Furthermore, we discuss the difference of this subfamily of SNXs from other subfamilies, such as SNX-BAR nexins (Bin-Amphiphysin-Rvs) that are associated with retromer or other retrieval complexes for the regulation of receptor signaling and membrane trafficking. Emerging evidence has shown that the dysregulation and malfunction of this subfamily of sorting nexins lead to various pathophysiological processes and disorders, including hypertension.

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Genetic determinants of ammonia-induced acute lung injury in mice

Cited by 7 publications

References 142 publications

Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study

Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study

Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease

SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking

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