title: Angiotensin II induces angiogenic factors production partly via AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells.
abstract: Angiotensin II (Ang II) has been shown to function as a key role in neovascularization of hepatocellular carcinoma (HCC), but little is known its underlying mechanisms. The aim of this study was to explore the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in Ang II-induced HCC angiogenic factors production. Herein, we found that Ang II upregulated angiogenic factors production such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Tie-2 in MHCC97H cells in a time- and concentration-dependent manner. And VEGF and Ang-2 caused a significant increase in angiogenic tube formation. Especially, Ang II-induced angiogenic tube formation was blunted by VEGF small interfering RNA (siRNA) and Ang-2 siRNA, respectively. The JAK2 inhibitor AG490 partly attenuated the effects of Ang II. Moreover, Ang II- induced JAK2 and STAT3 phosphorylation was significantly suppressed by losartan but not PD123319. Meanwhile, STAT3 phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression induced by Ang II were evidently impaired by AG490. More importantly, SOCS3 siRNA remarkably reinforced Ang II-induced VEGF, Ang-2 and Tie-2 generation in MHCC97H cells. Taken together, the present study demonstrates that Ang II induces angiogenic factors production partly via AT1/ JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells. These findings may provide important insights into the potential mechanism with respect to the AT1/ JAK2/ STAT3/SOCS3 signaling pathway associated with Ang II-induced angiogenesis in the pathogenesis of HCC.
authors.affiliation: Scientific Research Center, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. jiyuanyuan1234@163.com
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Wang
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Le
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D017931:DNA Primers; D044140:Receptor, Angiotensin, Type 1; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000804:Angiotensin II; C507924:JAK2 protein, human; D053614:Janus Kinase 2