1,25(OH)2D3 ameliorates high glucose-induced podocyte injury via PI3K/p-Akt signalling pathway / 中华肾脏病杂志

Objective To investigate the effect of 1,25(OH)2D3 on high glucose induced podocyte injury and its signal transduction mechanism.Methods Differentiated mouse podocytes were exposed to normal glucose,high glucose,and different concentrations of 1,25(OH)2D3 or LY294002 (a selective PI3K inhibitor) for 24 h.PCR and immunofluorescent staining were used to detect nephrin,podocin,and desmin.Western blotting was used to detect protein expression of nephrin,podocin,desmin,PI3K,Akt and p-Akt.Results Compared with high glucose group,1,25(OH)2D3 (100 nmol/L and 1000 nmol/L) significantly up-regulated the expression of podocin and nephrin in podocytes induced by high glucose (P ＜ 0.05).Meanwhile,1,25(OH)2D3 (100 nmol/L) significantly reduced the expression of desmin (P ＜ 0.05).PI3K and p-Akt were obviously reduced in high glucose group.In the presence of 1,25(OH)2D3,the trends were reversed.However the above effects of 1,25(OH)2D3 were abolished when p-Akt was blocked by the PI3K inhibitor LY294002.Conclusions 1,25 (OH)2D3 can inhibit high glucose-induced pedocyte injury through PI3K/p-Akt signaling pathway.

Semaphorin 4A enhances lung fibrosis through activation of Akt via PlexinD1 receptor.

Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including α-smooth muscle actin (α-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A treatment led to resistance to apoptosis in normal lung fibroblasts. Relative to normal lung fibroblasts, fibroblasts cultured from scars of patients with the fibrotic disease Systemic Sclerosis (SSc) showed elevated Sema4A secretion, enhanced α-SMA, ezrin, moesin, and paxillin expression, and high ability to induce collagen gel contraction. Using neutralizing antibody against Sema4A receptor, PlexinD1, we found that endogenous Sema4A signalling in SSc fibroblast was through PlexinD1 receptor. We then identified the signalling mechanism through which Sema4A-PlexinD1 promotes the ability of normal fibroblasts to contract a collagen gel matrix. Western blot analysis showed that Sema4A activated the Akt pathway in lung fibroblasts, and the specific inhibitor of Akt pathway, Akt inhibitor III, blocked the ability of Sema4A to promote the ability of lung fibroblasts to contract a collagen gel matrix. Thus, blocking Sema4APlexinD1- Akt cascades might be beneficial in reducing pulmonary fibrosis.

Dexmedetomidine protects cortical neurons from ketamine-induced apoptosis by activating the PI3 K-Akt signaling pathway / 医学研究生学报

Objective Dexmedetomidine is known to have a neuroprotective effect.The aim of this study was to investigate the effects of dexmedetomidine on ketamine-induced apoptosis of primarily cultured cortical neurons and its action mechanisms. Methods Rat cortical neurons were primarily cultured for 7 days and treated with ketamine (100μmol/L) and different concentrations of dexmedetomi-dine (0.001, 0.01, 0.1, and 1 μmol/L) for 24 hours, followed by measurement of the viability of the neurons by MTT assay.The neurons were divided into four groups:vehicle control, ketamine ( trea-ted with 100 μmol/L ketamine), dexmedetomidine+ketamine (DD+K, treated with 0.1 μmol/L DD and 100 μmol/L ketamine), and LY294002 ( treated with 0.1 μmol/L DD, 100 μmol/L ketamine, and 10 μmol/L LY294002) .After 24 hours of treatment, the apoptosis rate of the neurons was determined by Hoechst33258 staining, and the expressions of pAkt and cleaved-caspase-3 in the neu-rons detected by Western blot. Results The apoptosis rate of neurons was dramatically increased in the LY294002 and ketamine groups in comparison with the vehicle control and DD+K groups ([36.8 ±4.4] and [43.4 ±4.5]%vs [7.5 ±1.1] and [16.4 ± 3.6]%, P<0.01), the pAkt level remarkably decreased (0.26 ±0.02 and 0.15 ±0.01 vs 0.61 ±0.05 and 0.50 ±0.04, P<0.01), and the expression of cleaved caspase-3 significantly upregulated in the former two as compared with the latter two groups (0.40 ±0.02 and 0.65 ±0.03 vs 0.10 ±0.02 and 0.12 ±0.01, P<0.01). Conclusion Dexmedetomidine exerts a neuroprotec-tive effect against ketamine-induced apoptosis of neurons by activating the PI3K-Akt signaling pathway.