MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.

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MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.

Mol Immunol. 2015 Dec 31;70:84-93

Authors: Chen M, Huang L, Zhang W, Shi J, Lin X, Lv Z, Zhang W, Liang R, Jiang S

Abstract
BACKGROUND: Abnormal proliferation of ASM (airway smooth muscle) directly contributes to the airway remodeling during development of lung diseases such as asthma. Here we report that a specific microRNA (miR-23b) controls ASMCs proliferation through directly inhibiting TGF?R2/p-Smad3 pathway.
METHODS: The expression of miR-23b in ASMCs was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and apoptosis of ASMCs were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.
RESULTS: Overexpression of miR-23b significantly inhibited TGF-?1-induced ASMCs proliferation and promoted apoptosis. RT-PCR and Western blotting analysis showed miR-23b negatively regulates the expression of TGF?R2 and p-Smad3 in ASMCs. Subsequent analyses demonstrated that TGF?R2 was a direct and functional target of miR-23b, which was validated by the dual luciferase reporter assay.
CONCLUSIONS: MiR-23b may function as an inhibitor of airway smooth muscle cells proliferation through inactivation of TGF?R2/p-Smad3 pathway.

PMID: 26748386 [PubMed – as supplied by publisher]

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Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

Arch Dermatol Res. 2015 Nov 21;

Authors: Lesiak A, Sobolewska-Sztychny D, Majak P, Sobjanek M, Wodz K, Sygut KP, Majsterek I, Wozniacka A, Narbutt J

Abstract
In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

PMID: 26590974 [PubMed – as supplied by publisher]

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Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival.

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Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival.

J Immunol. 2015 May 1;

Authors: Al Heialy S, Zeroual M, Farahnak S, McGovern T, Risse PA, Novali M, Lauzon AM, Roman HN, Martin JG

Abstract
Contact between airway smooth muscle (ASM) cells and activated CD4(+) T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4(+) T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4(+) T cells. CD4(+) T cells, isolated from PBMCs of healthy subjects, when activated and cocultured with ASM cells for 24 h, formed nanotubes that were visualized by immunofluorescence and atomic force microscopy. Cell-to-cell transfer of the fluorescent dye calcein-AM confirmed cytoplasmic communication via nanotubes. Immunoreactive B cell lymphoma 2 (Bcl-2) and induced myeloid leukemia cell differentiation protein (Mcl-1), two major anti-apoptotic proteins, were present within the nanotubes. Downregulation of Mcl-1 by small interfering RNA in ASM cells significantly increased T cell apoptosis, whereas downregulation of Bcl-2 had no effect. Transfer of GFP-tagged Mcl-1 from ASM cells to CD4(+) T cells via the nanotubes confirmed directionality of transfer. In conclusion, activated T cells communicate with ASM cells via nanotube formation. Direct transfer of Mcl-1 from ASM to CD(+) T cells via nanotubes is involved in T cell survival. This study provides a novel mechanism of survival of CD4(+) T cells that is dependent on interaction with a structural cell.

PMID: 25934863 [PubMed – as supplied by publisher]

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Distinct Selectivity of Gangliosides Required for CD4(+) T and CD8(+) T Cell Activation.

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Distinct Selectivity of Gangliosides Required for CD4(+) T and CD8(+) T Cell Activation.

Biochim Biophys Acta. 2014 Sep 2;

Authors: Inokuchi JI, Nagafuku M, Ohno I, Suzuki A

Abstract
T cells compose a crucial part of the immune system and require activation. The first step of T cell activation is triggered by the movement of one of their surface molecules, known as T cell receptor, into localized regions of cell membrane known as lipid rafts. Molecules called gangliosides are known to be major components of lipid rafts, but their role in T-cell activation remains to be elucidated. This review summarizes recent findings that different types of T cells require distinct ganglioside types for the activation. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.

PMID: 25193136 [PubMed – as supplied by publisher]

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Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

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Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

Cochrane Database Syst Rev. 2014 Aug 2;8:CD003733

Authors: Knight-Madden JM, Hambleton IR

Abstract
BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome.
OBJECTIVES: To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2002) and Embase (1981 to 2002).Date of the most recent search of the Group’s Haemoglobinopathies Trials Register: 17 March 2014.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline.
DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease.
MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease.
AUTHORS’ CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.

PMID: 25086371 [PubMed – as supplied by publisher]

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