Possible divergence of serum-and glucocorticoid-inducible kinase function in ischemic brain injury

As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.

High Glucose Promotes the CTGF Expression in Human Mesangial Cells via Serum and Glucocorticoid-induced Kinase 1 Pathway

The role of serum and glucocorticoid-induced kinase 1 （SGK1） pathway in the connective tissue growth factor （CTGF） expression was investigated in cultured human mesangial cells （HMCs） under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with PIRES2-EGFP- S422D hSGK1 （SD） could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with PIRES2-EGFP （FP） under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with PIRES2-EGFP- K127N hSGK1 （KN） could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.

Effects of Glucocorticoid?Induced Transcript 1 Gene Deficiency on Glucocorticoid Activation in Asthmatic Mice

Background: Glucocorticoid (GC) is the first?line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid?induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown. Methods: A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV1) and GLCCI1 expression were detected. Asthma model was constructed in wild?type and GLCCI1 knockout (GLCCI1?/?) mice. Glucocorticoid receptor (GR) and mitogen?activated protein kinase phosphatase 1 (MKP?1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen?activated protein kinase (MAPK) was also detected by WB. Results: In asthmatic patients, the change of FEV1 was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP?1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild?type: GR: 0.769 vs. 1.000, P = 0.022; MKP?1: 0.493 vs. 1.000, P < 0.001. GLCCI1?/?: GR: 0.629 vs. 1.645, P < 0.001; MKP?1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP?1 mRNA expression levels than in asthmatic groups; however, GLCCI1?/?.asthmatic mice had less improvement (wild?type: GR: 1.517 vs. 0.769, P = 0.023; MKP?1: 1.036 vs. 0.493, P = 0.003. GLCCI1?/?: GR: 0.846 vs. 0.629, P = 0.116; MKP?1: 0.475 vs. 0.377, P = 0.388). GLCCI1?/? asthmatic mice had more obvious phosphorylation of p38 MAPK than wild?type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001). Conclusions: GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP?1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs.