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GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice.

Hao YE, He DF, Yin RH, Chen H, Wang J, Wang SX, Zhan YQ, Ge CH, Li CY, Yu M, Yang XM - FEBS Open Bio (2015)

Bottom Line: G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs).However, the functions of GIT2 in T cells have not yet been determined.Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Southern Medical University, Guangzhou, Guangdong Province, China ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

No MeSH data available.


Related in: MedlinePlus

The effect of GIT2 depletion on CCl4 induced liver injury. (A) Serum ALT and AST levels from Git2+/+ and Git2−/− mice (n = 3) were determined at 12 h following injection of CCl4 at the dosage of 1 ml/kg (1:3 diluted in corn oil) intraperitoneally (i.p.). (B) 12 h after 1 ml/kg (1:3 diluted in corn oil) CCl4 injection, mice were sacrificed and the liver tissues were fixed, sectioned and stained with H&E for histopathological and morphological analysis. Scare bar, 200 μm. The percentage of necrotic area was quantitated using ImageJ software and values are the mean ± SD of five fields of measurements.
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f0010: The effect of GIT2 depletion on CCl4 induced liver injury. (A) Serum ALT and AST levels from Git2+/+ and Git2−/− mice (n = 3) were determined at 12 h following injection of CCl4 at the dosage of 1 ml/kg (1:3 diluted in corn oil) intraperitoneally (i.p.). (B) 12 h after 1 ml/kg (1:3 diluted in corn oil) CCl4 injection, mice were sacrificed and the liver tissues were fixed, sectioned and stained with H&E for histopathological and morphological analysis. Scare bar, 200 μm. The percentage of necrotic area was quantitated using ImageJ software and values are the mean ± SD of five fields of measurements.

Mentions: To test whether GIT2 depletion also protects mice against chemically induced liver injury, Git2+/+ and Git2−/− mice were injected i.p. with CCl4. The results showed no significant differences in liver injury between Git2+/+ and Git2−/− mice (Fig. 2A and B), which may be due to a different mechanism of liver injury in this model, indicating the potential role of GIT2 in T cell-mediated liver injury.


GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice.

Hao YE, He DF, Yin RH, Chen H, Wang J, Wang SX, Zhan YQ, Ge CH, Li CY, Yu M, Yang XM - FEBS Open Bio (2015)

The effect of GIT2 depletion on CCl4 induced liver injury. (A) Serum ALT and AST levels from Git2+/+ and Git2−/− mice (n = 3) were determined at 12 h following injection of CCl4 at the dosage of 1 ml/kg (1:3 diluted in corn oil) intraperitoneally (i.p.). (B) 12 h after 1 ml/kg (1:3 diluted in corn oil) CCl4 injection, mice were sacrificed and the liver tissues were fixed, sectioned and stained with H&E for histopathological and morphological analysis. Scare bar, 200 μm. The percentage of necrotic area was quantitated using ImageJ software and values are the mean ± SD of five fields of measurements.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556731&req=5

f0010: The effect of GIT2 depletion on CCl4 induced liver injury. (A) Serum ALT and AST levels from Git2+/+ and Git2−/− mice (n = 3) were determined at 12 h following injection of CCl4 at the dosage of 1 ml/kg (1:3 diluted in corn oil) intraperitoneally (i.p.). (B) 12 h after 1 ml/kg (1:3 diluted in corn oil) CCl4 injection, mice were sacrificed and the liver tissues were fixed, sectioned and stained with H&E for histopathological and morphological analysis. Scare bar, 200 μm. The percentage of necrotic area was quantitated using ImageJ software and values are the mean ± SD of five fields of measurements.
Mentions: To test whether GIT2 depletion also protects mice against chemically induced liver injury, Git2+/+ and Git2−/− mice were injected i.p. with CCl4. The results showed no significant differences in liver injury between Git2+/+ and Git2−/− mice (Fig. 2A and B), which may be due to a different mechanism of liver injury in this model, indicating the potential role of GIT2 in T cell-mediated liver injury.

Bottom Line: G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs).However, the functions of GIT2 in T cells have not yet been determined.Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Southern Medical University, Guangzhou, Guangdong Province, China ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

No MeSH data available.


Related in: MedlinePlus