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Backgroud Angiotensin II (Ang II), a principal effector of renin-angiotensin system (RAS) and increased in aging tissues, can stimulate JAK/STAT pathway via the G-protein-coupled Ang II receptor type I (AT1) and induce nuclear translocation of signal transducers and activators of transcription (STAT). To further explore the role of Ang II in aging, we examined the effect of Ang II on human replicative senescent diploid fibroblast WI-38 cells. Methods Human senescent WI-38 cells were incubated with Ang II, receptor antagonist PD123319, valsartan, STAT3 sense plasmid, and/or STAT3 antisense plasmids. Methods were applied including electrophoretic mobility shift assay (EMSA), Western blot, transfection, and laser scanning confocal microscopy. Results It was found that cultured human senescent WI-38 cells constitutively expressed tissue inhibitor of metalloproteinase-1 (TIMP-1), and Ang II induced TIMP-1 protein expression in both time- and dose-dependent manners. Ang II induced STAT-DNA binding activity also in both time- and dose-dependent manners. And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins. STAT3 antisense oligonucleotides could inhibit both Ang II-induced STAT3-DNA binding activity as well as TMP-1 expression. Conclusion Ang II could up-regulate TIMP-1 expression through activating STAT3 signal pathway in human senescent cells, indicating that Ang II-STAT3-TIMP-1 pathway may be involved in the mechanism of sclerosis in aging tissues.
Backgroud Angiotensin II (Ang II), a principal effector of renin-angiotensin system (RAS) and increased in aging tissues, can stimulate JAK / STAT pathway via the G-protein-coupled Ang II receptor type I (AT1) and induce nuclear translocation of further signal transducers and activators of transcription (STAT). To further explore the role of Ang II in aging, we examined the effect of Ang II on human replicative senescent diploid fibroblast WI-38 cells. Methods Human senescent WI-38 cells were incubated with Ang II, receptor antagonist PD123319, valsartan, STAT3 sense plasmid, and / or STAT3 antisense plasmids. Methods were applied including electrophoretic mobility shift assay (EMSA), Western blot, transfection, and laser scanning confocal microscope. Results It was found that human human senescent WI-38 cells constitutively expressed tissue inhibitor of metalloproteinase-1 (TIMP-1), and Ang II induced TIMP-1 protein expression in both time-and dose-dependent manners. Ang II induced STAT-DNA b And supershift assay showed that the sis-inducing factor (SIF) band contained STAT3 proteins. STAT3 antisense oligonucleotides could inhibit both Ang II-induced STAT3-DNA binding activity as well as TMP -1 expression. Conclusion Ang II could up-regulate TIMP-1 expression through activating STAT3 signaling pathway in human senescent cells, indicating that Ang II-STAT3-TIMP-1 pathway may be involved in the mechanism of sclerosis in aging tissues.