{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:52:00Z","timestamp":1777434720088,"version":"3.51.4"},"reference-count":81,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Anemia of inflammation (AI), the second prevalent anemia, is associated with worse prognosis and increased mortality in numerous chronic diseases. We recently reported that the gasotransmitter hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) suppressed the inflammatory activation of signal transducer and activator of transcription 3 (STAT3) and hepcidin, the critical mediators of AI. Adenosine 5\u2032-monophosphate-activated protein kinase (AMPK) is a novel inflammatory regulator and might be activated by H\n                      <jats:sub>2<\/jats:sub>\n                      S. In this study, we determined whether AMPK played a role in H\n                      <jats:sub>2<\/jats:sub>\n                      S-mediated anti-inflammatory response in AI and evaluated the therapeutic potential of AMPK against AI by pharmacological and clinical approaches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We showed that AMPK mediated the inhibition of STAT3, hepcidin, and AI by H\n                      <jats:sub>2<\/jats:sub>\n                      S during inflammation. Moreover, pharmacological and genetic activation of AMPK ameliorated hepcidin production, corrected iron dysregulation, and relieved hypoferremia and anemia in both acute and chronic inflammation models in mice. Mechanistic studies indicated that AMPK suppressed STAT3\/hepcidin activation by promoting proteasome-mediated Janus kinase 2 (JAK2) degradation, which was dependent on the intact function of suppressor of cytokine signaling 1 (SOCS1) and increased interactions between SOCS1 and JAK2. Most importantly, the AMPK activator metformin was associated with decreased serum hepcidin content and anemia morbidity in Chinese type 2 diabetes mellitus patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This is the first study to demonstrate the inhibition of inflammatory hepcidin and AI by AMPK-induced JAK2 degradation. Our work uncovered AMPK as a novel therapeutic target, and metformin as a potential therapy against AI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The present work demonstrated that AMPK mediated the therapeutic effects of H\n                      <jats:sub>2<\/jats:sub>\n                      S and relieved AI by promoting SOCS1-mediated JAK2 degradation.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 27, 251\u2013268.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2016.6846","type":"journal-article","created":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T02:37:16Z","timestamp":1481078236000},"page":"251-268","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["AMPK Serves as a Therapeutic Target Against Anemia of Inflammation"],"prefix":"10.1177","volume":"27","author":[{"given":"Minjun","family":"Wang","sequence":"first","affiliation":[{"name":"Fudan University","place":["China"]},{"name":"Macau University of Science & Technology","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Xin","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Tang","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Li","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linling","family":"Fan","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Miao","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Tan","sequence":"additional","affiliation":[{"name":"Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiling","family":"Wang","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Zhun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]},{"name":"Macau University of Science & Technology","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,8,10]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2014.04.019"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3754"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60502-X"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.035"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.09.044"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07813"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.141"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010615)91:12<2214::AID-CNCR1251>3.0.CO;2-P"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.5.1118"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000066910.02844.D0"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1229"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.suppl_1.67"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2310"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00226.x"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.001"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(96)90130-4"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0672"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2009.06.001"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2491"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012512"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01854-5"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00396-2"},{"key":"e_1_3_4_24_2","first-page":"83","article-title":"Diabetes mellitus increases the severity of anemia in non-dialyzed patients with renal failure","volume":"11","author":"Ishimura E","year":"1997","unstructured":"Ishimura E, , Nishizawa Y, , Okuno S, , Matsumoto N, , Emoto M, , Inaba M, , Kawagishi T, , Kim C-W, , and Morii H. 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