Functional relevance of tetraspanin CD9 in vascular smooth muscle cell injury phenotypes: A novel target for the prevention of neointimal hyperplasia

Kotha, Jayaprakash; Zhang, Chunxiang; Longhurst, Celia M.; Lü, Yi; Jacobs, Jonathan D.; Cheng, Yunhui; Jennings, Lisa K.

doi:10.1016/j.atherosclerosis.2008.07.036

Cited by 20 publications

(31 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The COOH terminus of activated moesin links actin filaments and contributes to cell motility. CD9 is a member of the tetraspanin 4 superfamily of proteins that regulates cell motility in different cell types (15,35). Through a large extracellular domain, CD9 interacts with other proteins, allowing them to organize the cell surface into tetraspanin-enriched-microdomains (30).…”

Section: Go Biological Processes Involved In Hyperoxic Injury and Recmentioning

confidence: 99%

Protein expression profile of rat type two alveolar epithelial cells during hyperoxic stress and recovery

Bhargava

Dey²,

Becker

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

L604 -L614, 2013. First published September 6, 2013 doi:10.1152/ajplung.00079.2013.-In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized and are similar to changes in human acute respiratory distress syndrome. In the injured lung, alveolar type two (AT2) epithelial cells play a critical role in restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. We applied an unbiased systems-level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQ with tandem mass spectrometry. Of the 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene set enrichment analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A novel short time-series expression miner algorithm identified protein clusters with coherent changes during injury and repair. We concluded that coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung. alveolar epithelial cell proteome; acute respiratory distress syndrome; bioinformatics; hyperoxia HEALTHY RATS AND MICE EXPOSED to 100% oxygen develop respiratory failure and death within 2-3 days (2, 20). Histological examination of lungs from these animals shows pathological changes similar to those that occur in human acute respiratory distress syndrome (ARDS), with evidence of apoptosis and necrosis of the alveolar endothelium and epithelium (4, 20). There is evidence that hyperoxia is damaging to the human lung as well (8,24,33).Rodent lung morphology has been well characterized during acute oxygen-lung toxicity and subsequent recovery (19,20,58). In animals, exposure to normobaric hyperoxia for 72 h results in an exudative phase that is characterized by alveolar type I (AT1) epithelial cell death, swelling and necrosis of endothelial cells, interstitial edema, and filling of alveoli with an exudative fluid (19,33). Cessation of oxygen exposure after 60 h leads to a rapid decrease in the number of neutrophils within the first 3 days and an increase in the number of monocytes and lymphocytes, resulting in a normal differential of lung white blood cells by day 7 (58)...

show abstract

Section: Go Biological Processes Involved In Hyperoxic Injury and Recmentioning

confidence: 99%

Protein expression profile of rat type two alveolar epithelial cells during hyperoxic stress and recovery

Bhargava

Dey²,

Becker

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…The experimental design of plating the cells on FN in serumfree media was similar to multiple other studies that demonstrated ECM-mediated activation of EGFR in the absence of EGFR ligands [149][150][151]. Kotha, et al established that CD9 associates with integrin α5β1 using co-immunoprecipitation in multiple cell lines and that it plays a role in enhancing the activation state of β1 integrins [142,143].…”

Section: Chapter 4 Cd9 Contributions To Cancer Cell Biology * †mentioning

confidence: 89%

“…The pitfall to this hypothesis is that EGFR largely signals downstream through the p38MAPK, ERK pathway [152,153], but previous findings suggest PI3K is the major downstream signaling pathway from CD9 expression [142,143]. Although MMP-9 expression is primarily evoked through the PI3K pathway, there is sufficient evidence to suggest ERK signaling may also elicit MMP-9 expression [154][155][156].…”

Section: Chapter 4 Cd9 Contributions To Cancer Cell Biology * †mentioning

confidence: 99%

“…MMP-9 production was stimulated through the PI3K, Akt, JNK1/2 pathway in human limbal epithelial cell outgrowth and was not affected by MEK1/2 or p38MAPK inhibition [141].Lisa Jennings and colleagues previously demonstrated in two cell lines that CD9 expression enhances Akt phosphorylation [142,143]. Both of the CD9-elicited phenotypes were nullified upon treatment with LY294002 or wortmannin [142,143]. Preliminary studies with CD9-HT1080 cells indicated a 25% decrease in MMP-9 gelatinolytic band intensity using the PI3K inhibitor LY294002 in a gelatin zymography analysis of CD9-HT1080 conditioned media (Herr et al, unpublished observations).…”

Section: Chapter 4 Cd9 Contributions To Cancer Cell Biology * †mentioning

confidence: 99%

“…LY294002, wortmannin, and a dominant-negative Akt construct blocked MMP-9 production in multiple human hepatocellular carcinoma cell lines [133]. MMP-9 production was stimulated through the PI3K, Akt, JNK1/2 pathway in human limbal epithelial cell outgrowth and was not affected by MEK1/2 or p38MAPK inhibition [141].Lisa Jennings and colleagues previously demonstrated in two cell lines that CD9 expression enhances Akt phosphorylation [142,143]. Both of the CD9-elicited phenotypes were nullified upon treatment with LY294002 or wortmannin [142,143].…”

Section: Chapter 4 Cd9 Contributions To Cancer Cell Biology * †mentioning

confidence: 99%

See 2 more Smart Citations

Tetraspanin CD9: Contributions to Cancer Cell and Vascular Cell Phenotypes from the Sixth Man

Herr¹

View full text Add to dashboard Cite

The Functional Importance of Tetraspanins in Exosomes

Rana

Zöller

2012

Emerging Concepts of Tumor Exosome–Mediated Cell-Cell Communication

View full text Add to dashboard Cite

Exosomes are small vesicles that derive from the release of limiting membranes from multivesicular bodies (MVB). They carry and transfer selected membrane and cytoplasmic proteins, mRNA, and microRNA into target cells. Due to this shipping of information, exosomes are considered to be a most promising therapeutic tool for multiple diseases.Whereas knowledge on the composition of exosomes is rapidly increasing, the mode of selective recruitment into exosomes as well as target cell selection is poorly understood. We suggest that at least part of this task is taken over by tetraspanins. Tetraspanins are a highly conserved family of proteins that are involved in a multitude of biological processes. This is a sequel of their special arrangement in glycolipid-enriched membrane microdomains, where tetraspanins form a net between themselves and neighboring molecules. These membrane domains, called tetraspanin-enriched microdomains (TEM), are prone for internalization. The early endosomes become integrated into MVBs, the primary source of exosomes. Thereby tetraspanin and tetraspanin-associated molecules become enriched in exosomes.We will discuss here how the protein assembly of exosomes and possibly the recruitment of microRNA can be regulated by tetraspanins and how tetraspanins account for target cell selection and uptake of exosomes.Exosomes herald an unanticipated powerful path of cell-cell communication. An answer to how exosomes collect and transfer information will allow the use of nature's concept to cope with malfunctions. Abbreviations ADAMA disintegrin and metalloproteinase AP Adapter protein APC

show abstract

Functional relevance of tetraspanin CD9 in vascular smooth muscle cell injury phenotypes: A novel target for the prevention of neointimal hyperplasia

Cited by 20 publications

References 33 publications

Protein expression profile of rat type two alveolar epithelial cells during hyperoxic stress and recovery

Protein expression profile of rat type two alveolar epithelial cells during hyperoxic stress and recovery

Tetraspanin CD9: Contributions to Cancer Cell and Vascular Cell Phenotypes from the Sixth Man

The Functional Importance of Tetraspanins in Exosomes

Contact Info

Product

Resources

About