Mang II for 24 h and Zibotentan ZD4054 nuclear extracts were pr Parried and with regard to the activity of t of Stat3 DNA binding. A significant increase in Stat3 DNA-binding activity of t was in mesangial cells treated with Ang II or transfected with exogenous Ang II observed in relation to controlled The NG. Thus, these results showed that Ang II intracellular ht Re phosphorylation and Stat3 DNA-binding activity of t as well as increased. 3.5. R Of JAK2 in Ang II-induced intracellular Ren activation of Stat3. Jak2, a cytosolic tyrosine kinase is shown that the activation of latent cytoplasmic transcription factor Stat3 to cause mesangial cells. For this reason, the r Of JAK2 in the Ang II-induced intracellular Ren activation of Stat3 examined using JAK2 inhibitors such as AG 490 and Jak inhibitor I.
AG 490 is weight hlt Because mesangial cells has been shown to angiotensin II induced collagen IV protein synthesis and Erh increase the high glucose-induced TGF b1 and fibronectin synthesis by inhibiting the phosphorylation to prevent Stat3 tyrosine. Jak inhibitor I is a selective inhibitor of Jaks with much less effect on other kinases. 3.5.1. Effect of JAK2 inhibition on Stat3 effect BMS-536924 of protein expression AG 490th Mesangial cells were treated with 5 mM glucose or with 1 M NG contains exogenous Ang II or NG Mang Lt IImixed with a proteolytic juice incubated for 24 h. In separate groups of cells with exogenous Ang II and Ang II / proteotypic juice mixer and 10 M AG 490 for 24 h were incubated. At the end of the experiment, total cell lysates were prepared and analyzed for protein expression byWestern JAK2 and STAT3 blotting.
As shown in Figure 6, increases Jak2 and Stat3 exogenousAng ht II protein expression, w During Ang II increased Hte intracellular Re Stat3 protein has no effect on Jak2. Densitometric analysis of Western blots showed a significant increase in Stat3 protein in cells treated with Ang II or transfected with exogenous Ang II-NG compared with controls. Treatment with AG 490 inhibited Ang erh II-induced increase of exogenous Stat3 protein, but failed to block the increase in Stat3 protein expression in cells Ang IItransfected. These results suggest that the intracellular effects of angiotensin II on the Re Stat3 by an independent Ngigen Jak2 is mediated mechanism.
of candesartan, our results suggest that Ang II may be intracellular extracellular re physiological reactions without participation Ren Ang II signaling pathways that are activated by the cell membrane AT1 receptor to initiate. Most of the known effects of angiotensin II-induced extracellular Re Ang II via activation of AT1 receptors on the cell membrane. The binding of angiotensin II AT1 receptor L St many signaling pathways, including activation of tyrosine kinases, Jak and STAT family of latent cytoplasmic transcription factors. Ang II also stimulates the formation of complexes and Stat3 homo hetrodimers that the translocation into the nucleus and bind to specific DNA motifs in the activation of the gene for early growth response. Several studies of Marrero and Associates reported that the phosphorylation of JAK2 and STAT3 by Ang II is crucial for Ang II effects such as growth mediated activation of TGF b1, synthesis of matrix proteins And cell proliferation. In this study, an increase of Stat3 protein expression in mesangial cells with Feeder Treated lligen found