Suppression of JAK2/STAT3 Signaling Reduces End-to-End Arterial Anastomosis Induced Cell Proliferation in Common Carotid Arteries of Rats
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{"title"=>"Suppression of JAK2/STAT3 Signaling Reduces End-to-End Arterial Anastomosis Induced Cell Proliferation in Common Carotid Arteries of Rats", "type"=>"journal", "authors"=>[{"first_name"=>"Jinbing", "last_name"=>"Zhao", "scopus_author_id"=>"46462123200"}, {"first_name"=>"Meijuan", "last_name"=>"Zhang", "scopus_author_id"=>"56005241200"}, {"first_name"=>"Wei", "last_name"=>"Li", "scopus_author_id"=>"57196305919"}, {"first_name"=>"Xingfen", "last_name"=>"Su", "scopus_author_id"=>"45861653900"}, {"first_name"=>"Lin", "last_name"=>"Zhu", "scopus_author_id"=>"56544842500"}, {"first_name"=>"Chunhua", "last_name"=>"Hang", "scopus_author_id"=>"7103123538"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"368535223", "sgr"=>"84875021800", "doi"=>"10.1371/journal.pone.0058730", "scopus"=>"2-s2.0-84875021800", "pmid"=>"23516544"}, "id"=>"470dac29-b003-3025-8cb5-91f2612ffa97", "abstract"=>"BACKGROUND: JAK2/STAT3 pathway was reported to play an essential role in the neointima formation after vascular intima injury. However, little is known regarding this pathway to the whole layer injury after end-to-end arterial anastomosis (AA). Here, we investigated the role of JAK2/STAT3 pathway in common carotid arterial (CCA) anastomosis-induced cell proliferation, phenotypic change of vascular smooth muscle cells (VSMCs) and re-endothelialization.\\n\\nMETHODS: CCAs of adult male Wistar rats were resected at 3, 7, 14, and 30 days after end-to-end CCA anastomosis. Activation of JAK2/STAT3 pathway was detected by Western blotting and Immunofluorescence, and expression of proliferating cell nuclear antigen (PCNA) was detected by Q-PCR and Western blotting. Under the treatment with AG490 (a JAK2 inhibitor), protein levels of JAK2, STAT3 and PCNA, morphological changes of artery, phenotypic change of VSMCs, and re-endothelialization were measured by Western blotting, H&E, Q-PCR, and Evans blue staining respectively.\\n\\nRESULTS: The protein levels of p-JAK2, p-STAT3, and PCNA were up-regulated, peaked on the 7(th) day in the vessel wall after AA. AG490 down-regulated the levels of p-JAK2, p-STAT3, and PCNA on the 7(th)-day-group, resulting in reduced vessel wall proliferation on the 7(th) and 14(th) day after AA. Besides, AG490 switched the phenotypic change of VSMCs after AA representing inhibited mRNA levels of synthetic phase markers (osteopoitin and SMemb) and up-regulated contractile phase markers (ASMA, SM2 and SM22α). Furthermore, AG490 did not affect the re-endothelialization process on all indicated time points after AA (the 3(rd), 7(th), 14(th), and 30(th) day).\\n\\nCONCLUSION: Our study indicated that JAK2/STAT3 signaling pathway played an important role on cell proliferation of the injured vessel wall, and probably a promising target for the exploration of drugs increasing the patency or reducing the vascular narrowness after AA.", "link"=>"http://www.mendeley.com/research/suppression-jak2stat3-signaling-reduces-endtoend-arterial-anastomosis-induced-cell-proliferation-com", "reader_count"=>7, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Agricultural and Biological Sciences"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/988239"], "description"=>"<p>Quantification analysis of the blue staining area demonstrated heavy staining in and around the AA sites, which peaked at the 3<sup>rd</sup> day, and regressed to normal level at the 30<sup>th</sup> day after AA. No statistic difference was found between the AA+DMSO and AA+AG490 groups at all indicated time points. n = 3 anastomoses.</p>", "links"=>[], "tags"=>["aa"], "article_id"=>652768, "categories"=>["Physiology", "Medicine", "Neuroscience"], "users"=>["Jinbing Zhao", "Meijuan Zhang", "Wei Li", "Xingfen Su", "Lin Zhu", "Chunhua Hang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058730.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Re_endothelialization_assessment_on_AA_site_at_different_experimental_time_points_/652768", "title"=>"Re-endothelialization assessment on AA site at different experimental time points.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:28:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/988236"], "description"=>"<p><b>A</b>: AG490 down-regulated the activation of JAK2/STAT3 in the AA+AG490 group on the 7<sup>th</sup> day (n = 4 anastomoses). <b>B–D</b>: mRNA levels of PCNA were up-regulated after AA, and inhibited markedly after treating with AG490 on the 7<sup>th</sup> day. Protein levels of PCNA were increased and peaked at the 7<sup>th</sup> day after AA, and down-regulated in AA+AG490 group (n = 4 anastomoses). <b>E–F:</b> Morphometry analysis of CCA on the 7<sup>th</sup> and 14<sup>th</sup> day. Quantification analysis results were illustrated by the outside radius (R<sub>o</sub>)/inside radius (R<sub>i</sub>) ratio. Bar = 500 µm. n = 3 anastomoses. (<sup>*</sup> p<0.05 versus AA+AG490 group (7<sup>th</sup> day); <sup>**</sup> p<0.01 versus Sham group; ## p<0.01, §§ p<0.01; NS: no significant difference).</p>", "links"=>[], "tags"=>["inhibited", "up-regulation", "p-stat3", "attenuated", "proliferation"], "article_id"=>652765, "categories"=>["Physiology", "Medicine", "Neuroscience"], "users"=>["Jinbing Zhao", "Meijuan Zhang", "Wei Li", "Xingfen Su", "Lin Zhu", "Chunhua Hang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058730.g001", "stats"=>{"downloads"=>1, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AG490_inhibited_the_up_regulation_of_p_JAK2_p_STAT3_and_PCNA_and_attenuated_cell_proliferation_after_AA_/652765", "title"=>"AG490 inhibited the up-regulation of p-JAK2, p-STAT3 and PCNA, and attenuated cell proliferation after AA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:27:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/988233"], "description"=>"<p><b>A–F</b>: p-STAT3 positive cells (red) in Sham group and AA group determined by immunofluorecence (Samples: 7 days after AA; Arrows indicated the typical positive cells. n = 3 anastomoses. Bar = 100 µm). <b>G–I</b>: Representative bands of target proteins in Sham group and AA groups at 3, 7, and 14 days after surgery (n = 4 anastomoses). The analysis showed the expression p-JAK2 and p-STAT3 increased and peaked at 7 days after the AA procedure (<sup>**</sup> p<0.01 versus Sham group).</p>", "links"=>[], "tags"=>["surgery", "physiology", "neuroscience"], "article_id"=>652762, "categories"=>["Physiology", "Medicine", "Neuroscience"], "users"=>["Jinbing Zhao", "Meijuan Zhang", "Wei Li", "Xingfen Su", "Lin Zhu", "Chunhua Hang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058730.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_activation_features_of_JAK2_STAT3_in_the_vessel_wall_after_AA_/652762", "title"=>"activation features of JAK2/STAT3 in the vessel wall after AA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:27:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/988238"], "description"=>"<p>The mRNA levels of ASMA, SM2, and SM22α was lowered after AA, while that of osteopoitin and SMemb were raised markedly and peaked at 7<sup>th</sup> day after AA. At the 14<sup>th</sup> day time point, expression of SM2 and SM22α began to increase but still lower than Sham group, and expression of osteopoitin and SMemb decreased to lower levels. AG490 down-regulated the osteopoitin and SMemb expression, and had a trend to increase the ASMA and SM2 mRNA levels. All the results were normalized to Sham. n = 4 anastomoses. (<sup>*</sup> p<0.05, <sup>**</sup> p<0.01 versus AA+AG490 respectively).</p>", "links"=>[], "tags"=>["modulation", "vsmcs", "ag490", "aa"], "article_id"=>652767, "categories"=>["Physiology", "Medicine", "Neuroscience"], "users"=>["Jinbing Zhao", "Meijuan Zhang", "Wei Li", "Xingfen Su", "Lin Zhu", "Chunhua Hang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058730.g002", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypic_modulation_of_VSMCs_by_AG490_after_AA_procedure_/652767", "title"=>"Phenotypic modulation of VSMCs by AG490 after AA procedure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:28:28"}

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Relative Metric

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