Differential expression of integrin α subunits supports distinct roles during lung branching morphogenesis

Wu, Justina E.; Santoro, Samuel A.

doi:10.1002/(sici)1097-0177(199606)206:2<169::aid-aja6>3.0.co;2-g

Cited by 47 publications

(40 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALDH1 is located in the bronchial epithelium and alveolar parenchyma, and its temporal and spatial expression is associated with alveolar septation and postnatal lung development (Hind et al, 2002). The epithelial expression of ITGA2 is restricted to branch tips, and its spatial and temporal expression is associated with high level of expression of collagen mRNA (Coraux et al, 1998;Wu and Santoro, 1996), which is necessary for branching to occur normally. SOD2 null mutant mice show abnormalities in saccules as a result of delayed postnatal lung development (Asikainen et al, 2002;Tsan et al, 1998).…”

Section: Park Et Almentioning

confidence: 99%

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Park

Lai²,

Samuel³

et al. 2011

Cellular Reprogramming

View full text Add to dashboard Cite

Although numerous mammalian species have been successfully cloned by somatic cell nuclear transfer (SCNT), little is known about gene expression of cloned pigs by SCNT. In the present study, expression profiles of 1-month-old cloned pigs generated from fetal fibroblasts (n ¼ 5) were compared to those of age-matched controls (n ¼ 5) using a 13K oligonucleotide microarray. The brain, kidney, and lung were chosen for microarray analysis to represent tissues from endoderm, mesoderm, and ectoderm in origin. In clones, 179 and 154 genes were differentially expressed in the kidney and the lung, respectively (fold change >2, p < 0.05, false discovery rate ¼ 0.05), whereas only seven genes were differentially expressed in the brain of clones. Functional analysis of the differentially expressed genes revealed that they were enriched in diabetic nephropathy in the kidney, delayed alveologenesis as well as downregulated MAPK signaling pathways in the lung, which was accompanied with collapsed alveoli in the histological examination of the lung. To evaluate whether the gene expression anomalies are associated with changes in DNA methylation, global concentration of the methylated cytosine was measured in lung DNA by HPLC. Clones were significantly hypermethylated (5.72%) compared to the controls (4.13%). Bisulfite-pyrosequencing analyses of the promoter regions of differentially expressed genes, MYC and Period 1 (PER1), however, did not show any differences in the degree of DNA methylation between controls and clones. Together, these findings demonstrate that cloned pigs have altered gene expression that may potentially cause organ dysfunction.

show abstract

Section: Park Et Almentioning

confidence: 99%

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Park

Lai²,

Samuel³

et al. 2011

Cellular Reprogramming

View full text Add to dashboard Cite

show abstract

“…Normal epithelial organization is dependent upon speci®c cell adhesion involving Ecadherin, actin cytoskeletal-associated proteins, and integrins and the decreased expression of E-cadherin and integrins occur in breast and prostate carcinomas, and this decrease correlates with increased invasiveness (Oka et al, 1993;Zutter et al, 1993). Epithelial tubulogenesis is responsible for the intricate organization of parenchymal organs such as the lung and mammary gland where elongation and branching of epithelial tubules is critical for organ formation (Wu and Santoro, 1996). During development new epithelia usually arise from existing ones but mesenchymal cells are the source of new epithelial cells during organogenesis of the kidney, ovary and testis.…”

Section: Introductionmentioning

confidence: 99%

A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer

et al. 1997

View full text Add to dashboard Cite

The ETS family of genes are implicated in cancers such as Ewings sarcoma, acute myeloid leukemia and chronic myelomoncytic leukemia. Further, they have important functions in embryonic development. Hence, identi®ca-tion and characterization of members of this family are important. We identify a novel ETS family member, ELF3, and report its human and murine cDNA sequences. The mouse cDNA has an alternatively spliced transcript with an extra 60 bp inserted. Hence we present the organization of the murine Elf3 gene together with its exon/intron structure. This gene consists of 9 exons and 8 introns spanning 4.8 kb. ELF3 binds and transactivates ETS sequences and interestingly also shows the ability to bind a GGAT-like purine core, a preferential ETS1/ETS2 type binding site. The expression of ELF3, unlike most other ETS family members, is absent in hematopoietic cells and hematopoietic organs in humans and mice. Intriguingly, the gene is speci®cally expressed in cell lines of epithelial origin and in organs such as lung, stomach, intestine, kidney that have specialized epithelial cells. We localize the human gene to 1q32.2, a region that is ampli®ed in epithelial tumors of the breast, lung and prostate. Finally, we show that ELF3 expression is increased in a lung carcinoma and adenocarcinoma, as compared to normal tissue. ELF3 is also expressed in cell lines derived from lung cancers. These results suggest that this novel ETS gene may be involved in lung tumorigenesis.

show abstract

“…Given that α6 is expressed in embryonic endothelium from around E13.5 onwards [42][43][44], the fact that the α6fl/fl-Tie1Cre+ mice are born at normal Mendelian ratios suggests that the embryos either lack or overcome any gross angiogenic defect. Our data showing enhanced angiogenesis after endothelial α6-integrin deletion is somewhat reminiscent of the effect of β3-integrin deletion in mice, where global deletion of β3-integrins enhances tumour growth, tumour angiogenesis, and endothelial VEGFR2 levels [30,33,45].…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of the alpha 6‐integrin subunit in Tie1Cre mice enhances tumour angiogenesis

Germain

Arcangelis

Robinson

et al. 2009

The Journal of Pathology

View full text Add to dashboard Cite

Laminins are expressed highly in blood vessel basement membranes and have been implicated in angiogenesis. α6β1-and α6β4-integrins are major receptors for laminins in endothelial cells, but the precise role of endothelial α6-integrin in tumour angiogenesis is not clear. We show that blood vessels in human invasive ductal carcinoma of the breast have decreased expression of the α6-integrin-subunit when compared with normal breast tissue. These data suggest that a decrease in α6-integrin-subunit expression in endothelial cells is associated with tumour angiogenesis. To test whether the loss of the endothelial α6-integrin subunit affects tumour growth and angiogenesis, we generated α6fl/fl-Tie1Cre+ mice and showed that endothelial deletion of α6-integrin is sufficient to enhance tumour size and tumour angiogenesis in both murine B16F0 melanoma and Lewis cell lung carcinoma. Mechanistically, endothelial α6-integrin deficiency elevated significantly VEGF-mediated angiogenesis both in vivo and ex vivo. In particular, α6-integrin-deficient endothelial cells displayed increased levels of VEGF-receptor 2 (VEGFR2) and VEGF-mediated downstream ERK1/2 activation. By developing the first endothelial-specific α6-knockout mice, we show that the expression of the α6-integrin subunit in endothelial cells acts as a negative regulator of angiogenesis both in vivo and ex vivo.

show abstract

Differential expression of integrin α subunits supports distinct roles during lung branching morphogenesis

Cited by 47 publications

References 60 publications

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

Altered Gene Expression Profiles in the Brain, Kidney, and Lung of One-Month-Old Cloned Pigs

A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer

Genetic ablation of the alpha 6‐integrin subunit in Tie1Cre mice enhances tumour angiogenesis

Contact Info

Product

Resources

About