A Role for Forkhead Box A1 in Acute Lung Injury

Song, Lan; Zhang, Bin; Feng, Yan; Luo, Xin; Wei, Xing; Xiao, Xianzhong

doi:10.1007/s10753-009-9139-x

Cited by 18 publications

(8 citation statements)

References 44 publications

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“…Specifically, it has been shown to play a pro-apoptotic role during oxidative-stress induced apoptosis in type II pneumocytes. 33 Over-expression of FOXA1 has been shown to promote apoptosis, 34 which has been implicated as a mechanism contributing to COPD and emphysema progression. 35 We demonstrate expression of FOXA1 protein in airway epithelium and lung parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

et al. 2012

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Rationale Accelerated lung function decline is a key COPD phenotype; however its genetic control remains largely unknown. Methods We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European-American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Measurements and Main Results Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. Conclusions We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility.

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Section: Discussionmentioning

confidence: 99%

Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

et al. 2012

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“…Loss of Foxa1 also decreased the expression of lung differentiation markers [e.g. FOXA1 expression is increased in a rat model of ALI (acute lung injury), in which it is suggested to function in alveolar type II epithelial cell apoptosis [41], and is similarly necessary for H 2 O 2 -induced apoptosis in A549 cells [42]. This is at least partly due to the dependency of both CCSP (Scbg1a1) [35] and SP-B (Sftpb) [36,37] promoters on FOXA1 for activation in lung epithelium.…”

Section: Lungmentioning

confidence: 99%

FOXA1: a transcription factor with parallel functions in development and cancer

2011

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When aberrant, factors critical for organ morphogenesis are also commonly involved in disease progression. FOXA1 (forkhead box A1), also known as HNF3α (hepatocyte nuclear factor 3α), is required for postnatal survival due to its essential role in controlling pancreatic and renal function. In addition to regulating a variety of tissues during embryogenesis and early life, rescue experiments have revealed a specific role for FOXA1 in the postnatal development of the mammary gland and prostate. Activity of the nuclear hormone receptors ERα (oestrogen receptor α) and AR (androgen receptor) is also required for proper development of the mammary gland and prostate respectively. FOXA1 modulates ER and AR function in breast and prostate cancer cells, supporting the postulate that FOXA1 is involved in ER and AR signalling under normal conditions, and that some carcinogenic processes in these tissues stem from hormonally regulated developmental pathways gone awry. In addition to broadly reviewing the function of FOXA1 in various aspects of development and cancer, this review focuses on the interplay of FOXA1/ER and FOXA1/AR, in normal and cancerous mammary and prostate epithelial cells. Given the hormone dependency of both breast and prostate cancer, a thorough understanding of FOXA1's role in both cancer types is critical for battling hormone receptor-positive disease and acquired anti-hormone resistance.

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“…FoXa1 is a member of the winged-helix family of transcription factors and shares structural similarities with FoXa2 and FoXa3. Song et al (14) reported that the overexpression of FoXa1 promoted pulmonary epithelial cell apoptosis in ali. Whether MalaT1 acts as a cerna for the mir-17-5p/FoXa1 axis, consequently regulating cell proliferation and apoptosis, in lPS-induced a549, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of the lncRNA MALAT1 alleviates lipopolysaccharide‑induced A549 cell injury by targeting the miR‑17‑5p/FOXA1 axis

et al. 2019

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long-noncoding rnas (lncrnas) are crucial for the pathophysiology of acute lung injury (ali). Metastasis-associated lung adenocarcinoma transcript 1 (MalaT1) suppresses inf lammatory responses via microrna (mir)-146a in lipopolysaccharide (lPS)-induced ali. However, the molecular mechanisms underlying the MalaT1-mediated regulation of cell proliferation and apoptosis in lPS-induced ali remain unclear. in the present study, it was found that lPS treatment upregulated MalaT1 expression and suppressed the proliferation of a549 cells. MalaT1 knockdown significantly promoted the proliferation and G1/S phase transition and inhibited apoptosis in lPS-treated a549 cells. in addition, mir-17-5p was a direct target of MalaT1. mir-17-5p expression was downregulated and FoXa1 expression was upregulated in lPS-treated a549 cells. Further, MalaT1 knockdown promoted mir-17-5p expression and inhibited FoXa1 expression, whereas the combined suppression of MalaT1 and mir-17-5p induced FoXa1 expression. Moreover, mir-17-5p knockdown reversed the effects of MalaT1 suppression on lPS-induced a549 cell proliferation. These results indicated that MalaT1 serves as a competing endogenous lncrna that, by sequestering mir-17-5p, stimulates FoXa1 expression and mediates lPS-induced a549 cell injury. in conclusion, the present study demonstrated that MalaT1 knockdown alleviates lPS-induced a549 cell injury by targeting the mir-17-5p/FoXa1 axis.

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A Role for Forkhead Box A1 in Acute Lung Injury

Cited by 18 publications

References 44 publications

Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

FOXA1: a transcription factor with parallel functions in development and cancer

Knockdown of the lncRNA MALAT1 alleviates lipopolysaccharide‑induced A549 cell injury by targeting the miR‑17‑5p/FOXA1 axis

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