{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:56:45Z","timestamp":1790290605287,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270118"],"award-info":[{"award-number":["81270118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570052"],"award-info":[{"award-number":["81570052"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule \u03b2 (RELM-\u03b2) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-\u03b2 has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-\u03b2 in HPH remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-\u03b2 in a rat HPH model and in hPASMCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overexpression of RELM-\u03b2 caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVH\n                      <jats:underline>I<\/jats:underline>\n                      ) and thickening of small pulmonary arterioles. Knockdown of RELM-\u03b2 partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-\u03b2 gene overexpression or silencing, respectively. Recombinant RELM-\u03b2 protein increased the intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-\u03b2 on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that RELM-\u03b2 acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-\u03b2 are likely to be mediated by the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -dependent PI3K\/Akt\/mTOR and PKC\/MAPK pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-020-01598-4","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T16:03:31Z","timestamp":1609949011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Resistin-like molecule \u03b2 acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K\/Akt\/mTOR and PKC\/MAPK signaling pathways"],"prefix":"10.1186","volume":"22","author":[{"given":"Heshen","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruicheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianzhi","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiguo","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"issue":"7","key":"1598_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1161\/01.RES.0000243584.45145.3f","volume":"99","author":"KR Stenmark","year":"2006","unstructured":"Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006;99(7):675\u201391.","journal-title":"Circ Res"},{"issue":"Suppl 14","key":"1598_CR2","doi-asserted-by":"publisher","first-page":"S1789","DOI":"10.21037\/jtd.2019.08.54","volume":"11","author":"S Sahay","year":"2019","unstructured":"Sahay S. Evaluation and classification of pulmonary arterial hypertension. J Thorac Dis. 2019;11(Suppl 14):S1789\u201399.","journal-title":"J Thorac Dis"},{"issue":"Suppl 23","key":"1598_CR3","doi-asserted-by":"publisher","first-page":"S2763","DOI":"10.21037\/jtd.2018.07.63","volume":"10","author":"I Opitz","year":"2018","unstructured":"Opitz I, Ulrich S. Pulmonary hypertension in chronic obstructive pulmonary disease and emphysema patients: prevalence, therapeutic options and pulmonary circulatory effects of lung volume reduction surgery. J Thorac Dis. 2018;10(Suppl 23):S2763\u201374.","journal-title":"J Thorac Dis"},{"issue":"2","key":"1598_CR4","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1183\/09031936.00148310","volume":"38","author":"A Campo","year":"2011","unstructured":"Campo A, Mathai SC, Le Pavec J, et al. Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension. Eur Respir J. 2011;38(2):359\u201367.","journal-title":"Eur Respir J"},{"issue":"2","key":"1598_CR5","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1513\/AnnalsATS.201509-599FR","volume":"13","author":"T Thenappan","year":"2016","unstructured":"Thenappan T, Prins KW, Pritzker MR, Scandurra J, Volmers K, Weir EK. The critical role of pulmonary arterial compliance in pulmonary hypertension. Ann Am Thorac Soc. 2016;13(2):276\u201384.","journal-title":"Ann Am Thorac Soc"},{"issue":"2","key":"1598_CR6","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1097\/FJC.0000000000000328","volume":"67","author":"MX Li","year":"2016","unstructured":"Li MX, Jiang DQ, Wang Y, et al. Signal mechanisms of vascular remodeling in the development of pulmonary arterial hypertension. J Cardiovasc Pharmacol. 2016;67(2):182\u201390.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"2","key":"1598_CR7","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1073\/pnas.98.2.502","volume":"98","author":"CM Steppan","year":"2001","unstructured":"Steppan CM, Brown EJ, Wright CM, et al. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA. 2001;98(2):502\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"1598_CR8","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.bbrc.2003.09.093","volume":"310","author":"RZ Yang","year":"2003","unstructured":"Yang RZ, Huang Q, Xu A, et al. Comparative studies of resistin expression and phylogenomics in human and mouse. Biochem Biophys Res Commun. 2003;310(3):927\u201335.","journal-title":"Biochem Biophys Res Commun"},{"issue":"10","key":"1598_CR9","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1161\/01.RES.0000073999.07698.33","volume":"92","author":"X Teng","year":"2003","unstructured":"Teng X, Li D, Champion HC, Johns RA. FIZZ1\/RELMalpha, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties. Circ Res. 2003;92(10):1065\u20137.","journal-title":"Circ Res"},{"issue":"6","key":"1598_CR10","doi-asserted-by":"publisher","first-page":"L1159","DOI":"10.1152\/ajplung.00168.2006","volume":"291","author":"K Yamaji-Kegan","year":"2006","unstructured":"Yamaji-Kegan K, Su Q, Angelini DJ, Champion HC, Johns RA. Hypoxia-induced mitogenic factor has proangiogenic and proinflammatory effects in the lung via VEGF and VEGF receptor-2. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1159\u201368.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"9","key":"1598_CR11","doi-asserted-by":"publisher","first-page":"5539","DOI":"10.4049\/jimmunol.0904021","volume":"185","author":"K Yamaji-Kegan","year":"2010","unstructured":"Yamaji-Kegan K, Su Q, Angelini DJ, Myers AC, Cheadle C, Johns RA. Hypoxia-induced mitogenic factor (HIMF\/FIZZ1\/RELMalpha) increases lung inflammation and activates pulmonary microvascular endothelial cells via an IL-4-dependent mechanism. J Immunol. 2010;185(9):5539\u201348.","journal-title":"J Immunol"},{"issue":"3","key":"1598_CR12","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/j.febslet.2006.01.012","volume":"580","author":"A Renigunta","year":"2006","unstructured":"Renigunta A, Hild C, Rose F, et al. Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia. FEBS Lett. 2006;580(3):900\u20133.","journal-title":"FEBS Lett"},{"issue":"1","key":"1598_CR13","doi-asserted-by":"publisher","first-page":"450","DOI":"10.4049\/jimmunol.1000964","volume":"187","author":"T Liu","year":"2011","unstructured":"Liu T, Baek HA, Yu H, et al. FIZZ2\/RELM-\u03b2 induction and role in pulmonary fibrosis. J Immunol. 2011;187(1):450\u201361.","journal-title":"J Immunol"},{"issue":"5","key":"1598_CR14","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1165\/rcmb.2008-0271OC","volume":"41","author":"DJ Angelini","year":"2009","unstructured":"Angelini DJ, Su Q, Yamaji-Kegan K, et al. Resistin-like molecule-beta in scleroderma-associated pulmonary hypertension. Am J Respir Cell Mol Biol. 2009a;41(5):553\u201361.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"12","key":"1598_CR15","doi-asserted-by":"publisher","first-page":"L1090","DOI":"10.1152\/ajplung.00279.2013","volume":"306","author":"K Yamaji-Kegan","year":"2014","unstructured":"Yamaji-Kegan K, Takimoto E, Zhang A, et al. Hypoxia-induced mitogenic factor (FIZZ1\/RELMalpha) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014;306(12):L1090\u2013103.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"2","key":"1598_CR16","doi-asserted-by":"publisher","first-page":"L263","DOI":"10.1152\/ajplung.90416.2008","volume":"297","author":"C Fan","year":"2009","unstructured":"Fan C, Su Q, Li Y, et al. Hypoxia-induced mitogenic factor\/FIZZ1 induces intracellular calcium release through the PLC-IP(3) pathway. Am J Physiol Lung Cell Mol Physiol. 2009;297(2):L263\u201370.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1598_CR17","doi-asserted-by":"publisher","first-page":"117419","DOI":"10.1016\/j.lfs.2020.117419","volume":"246","author":"L Han","year":"2020","unstructured":"Han L, Song N, Hu X, et al. Inhibition of RELM-beta prevents hypoxia-induced overproliferation of human pulmonary artery smooth muscle cells by reversing PLC-mediated KCNK3 decline. Life Sci. 2020;246:117419.","journal-title":"Life Sci"},{"issue":"4","key":"1598_CR18","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","volume":"170","author":"DA Fruman","year":"2017","unstructured":"Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605\u201335.","journal-title":"Cell"},{"issue":"5","key":"1598_CR19","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1002\/jcb.21657","volume":"104","author":"SH Lee","year":"2008","unstructured":"Lee SH, Lee MY, Lee JH, Han HJ. A potential mechanism for short time exposure to hypoxia-induced DNA synthesis in primary cultured chicken hepatocytes: correlation between Ca(2+)\/PKC\/MAPKs and PI3K\/Akt\/mTOR. J Cell Biochem. 2008;104(5):1598\u2013611.","journal-title":"J Cell Biochem"},{"issue":"1","key":"1598_CR20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/jcp.22091","volume":"224","author":"JM Ryu","year":"2010","unstructured":"Ryu JM, Lee MY, Yun SP, Han HJ. High glucose regulates cyclin D1\/E of human mesenchymal stem cells through TGF-beta1 expression via Ca2+\/PKC\/MAPKs and PI3K\/Akt\/mTOR signal pathways. J Cell Physiol. 2010;224(1):59\u201370.","journal-title":"J Cell Physiol"},{"issue":"5","key":"1598_CR21","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1161\/HYPERTENSIONAHA.116.08743","volume":"69","author":"X Zeng","year":"2017","unstructured":"Zeng X, Zhu L, Xiao R, et al. Hypoxia-induced mitogenic factor acts as a nonclassical ligand of calcium-sensing receptor, therapeutically exploitable for intermittent hypoxia-induced pulmonary hypertension. Hypertension. 2017;69(5):844\u201354.","journal-title":"Hypertension"},{"issue":"1","key":"1598_CR22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3892\/ijmm.2015.2209","volume":"36","author":"Y Jiang","year":"2015","unstructured":"Jiang Y, Wang J, Tian H, et al. Increased SUMO-1 expression in response to hypoxia: interaction with HIF-1\u03b1 in hypoxic pulmonary hypertension. Int J Mol Med. 2015;36(1):271\u201381.","journal-title":"Int J Mol Med"},{"key":"1598_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1465-9921-14-1","volume":"14","author":"DJ Angelini","year":"2013","unstructured":"Angelini DJ, Su Q, Yamaji-Kegan K, et al. Hypoxia-induced mitogenic factor (HIMF\/FIZZ1\/RELMalpha) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling. Respir Res. 2013;14:1.","journal-title":"Respir Res"},{"issue":"4","key":"1598_CR24","doi-asserted-by":"publisher","first-page":"L582","DOI":"10.1152\/ajplung.90526.2008","volume":"296","author":"DJ Angelini","year":"2009","unstructured":"Angelini DJ, Su Q, Yamaji-Kegan K, et al. Hypoxia-induced mitogenic factor (HIMF\/FIZZ1\/RELMalpha) induces the vascular and hemodynamic changes of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2009b;296(4):L582\u201393.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"6","key":"1598_CR25","doi-asserted-by":"publisher","first-page":"L574","DOI":"10.1152\/ajplung.00327.2013","volume":"306","author":"R Zhang","year":"2014","unstructured":"Zhang R, Shi L, Zhou L, et al. Transgelin as a therapeutic target to prevent hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014;306(6):L574\u201383.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1598_CR26","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.biochi.2018.12.004","volume":"158","author":"Y Jiang","year":"2019","unstructured":"Jiang Y, Zhou Y, Peng G, et al. TRPC channels mediated calcium entry is required for proliferation of human airway smooth muscle cells induced by nicotine-nAChR. Biochimie. 2019;158:139\u201348.","journal-title":"Biochimie"},{"issue":"2","key":"1598_CR27","doi-asserted-by":"publisher","first-page":"L305","DOI":"10.1152\/ajplung.00147.2007","volume":"293","author":"A Mishra","year":"2007","unstructured":"Mishra A, Wang M, Schlotman J, et al. Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L305\u201313.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"51","key":"1598_CR28","doi-asserted-by":"publisher","first-page":"42016","DOI":"10.1074\/jbc.M503065200","volume":"280","author":"A Kushiyama","year":"2005","unstructured":"Kushiyama A, Shojima N, Ogihara T, et al. Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet. J Biol Chem. 2005;280(51):42016\u201325.","journal-title":"J Biol Chem"},{"issue":"2","key":"1598_CR29","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1183\/09031936.00107811","volume":"39","author":"C Fang","year":"2012","unstructured":"Fang C, Meng Q, Wu H, et al. Resistin-like molecule-beta is a human airway remodelling mediator. Eur Respir J. 2012;39(2):458\u201366.","journal-title":"Eur Respir J"},{"issue":"15","key":"1598_CR30","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.1093\/emboj\/19.15.4046","volume":"19","author":"IN Holcomb","year":"2000","unstructured":"Holcomb IN, Kabakoff RC, Chan B, et al. FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J. 2000;19(15):4046\u201355.","journal-title":"EMBO J"},{"issue":"7","key":"1598_CR31","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1111\/j.1440-1843.2012.02215.x","volume":"17","author":"C Grainge","year":"2012","unstructured":"Grainge C, Dulay V, Ward J, et al. Resistin-like molecule-\u03b2 is induced following bronchoconstriction of asthmatic airways. Respirology. 2012;17(7):1094\u2013100.","journal-title":"Respirology"},{"issue":"5","key":"1598_CR32","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1111\/cea.12481","volume":"45","author":"CL Fang","year":"2015","unstructured":"Fang CL, Yin LJ, Sharma S, et al. Resistin-like molecule-\u03b2 (RELM-\u03b2) targets airways fibroblasts to effect remodelling in asthma: from mouse to man. Clin Exp Allergy. 2015;45(5):940\u201352.","journal-title":"Clin Exp Allergy"},{"key":"1598_CR33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1465-9921-7-37","volume":"7","author":"Q Tong","year":"2006","unstructured":"Tong Q, Zheng L, Lin L, et al. VEGF is upregulated by hypoxia-induced mitogenic factor via the PI-3K\/Akt-NF-kappaB signaling pathway. Respir Res. 2006;7:37.","journal-title":"Respir Res"},{"key":"1598_CR34","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.biocel.2018.08.005","volume":"105","author":"Y Jiang","year":"2018","unstructured":"Jiang Y, Zhou X, Hu R, Dai A. TGF-\u03b21-induced SMAD2\/3\/4 activation promotes RELM-\u03b2 transcription to modulate the endothelium-mesenchymal transition in human endothelial cells. Int J Biochem Cell Biol. 2018;105:52\u201360.","journal-title":"Int J Biochem Cell Biol"},{"issue":"3","key":"1598_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1164\/rccm.200912-1827ED","volume":"181","author":"RA Johns","year":"2010","unstructured":"Johns RA. Th2 inflammation, hypoxia-induced mitogenic factor\/FIZZ1, and pulmonary hypertension and vascular remodeling in schistosomiasis. Am J Respir Crit Care Med. 2010;181(3):203\u20135.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"1598_CR36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s11936-019-0718-3","volume":"21","author":"KV Woo","year":"2019","unstructured":"Woo KV, Ornitz DM, Singh GK. Diagnosis and pathophysiological mechanisms of group 3 hypoxia-induced pulmonary hypertension. Curr Treat Options Cardiovasc Med. 2019;21(3):16.","journal-title":"Curr Treat Options Cardiovasc Med"},{"issue":"1","key":"1598_CR37","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1161\/ATVBAHA.115.306710","volume":"36","author":"RA Johns","year":"2016","unstructured":"Johns RA, Takimoto E, Meuchel LW, et al. Hypoxia-inducible factor 1alpha is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1\/RELMalpha)-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2016;36(1):134\u201344.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"2","key":"1598_CR38","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.118.10845","volume":"72","author":"S Kumar","year":"2018","unstructured":"Kumar S, Wang G, Liu W, et al. Hypoxia-induced mitogenic factor promotes cardiac hypertrophy via calcium-dependent and hypoxia-inducible factor-1alpha mechanisms. Hypertension. 2018;72(2):331\u201342.","journal-title":"Hypertension"},{"issue":"12","key":"1598_CR39","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1161\/ATVBAHA.119.313535","volume":"39","author":"O Boucherat","year":"2019","unstructured":"Boucherat O, Paulin R, Provencher S, Bonnet S. New insights into HIMF (hypoxia-induced mitogenic factor)-mediated signaling pathways in pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2019;39(12):2451\u20133.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"1598_CR40","doi-asserted-by":"publisher","first-page":"H1546","DOI":"10.1152\/ajpheart.00944.2011","volume":"302","author":"FK Kuhr","year":"2012","unstructured":"Kuhr FK, Smith KA, Song MY, Levitan I, Yuan JX. New mechanisms of pulmonary arterial hypertension: role of Ca2+ signaling. Am J Physiol Heart Circ Physiol. 2012;302(8):H1546\u201362.","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"7","key":"1598_CR41","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1002\/ibd.20420","volume":"14","author":"RB Krimi","year":"2008","unstructured":"Krimi RB, Kotelevets L, Dubuquoy L, et al. Resistin-like molecule beta regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice. Inflamm Bowel Dis. 2008;14(7):931\u201341.","journal-title":"Inflamm Bowel Dis"},{"issue":"3","key":"1598_CR42","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1165\/rcmb.2003-0319OC","volume":"31","author":"KF Wagner","year":"2004","unstructured":"Wagner KF, Hellberg AK, Balenger S, et al. Hypoxia-induced mitogenic factor has antiapoptotic action and is upregulated in the developing lung: coexpression with hypoxia-inducible factor-2alpha. Am J Respir Cell Mol Biol. 2004;31(3):276\u201382.","journal-title":"Am J Respir Cell Mol Biol"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-020-01598-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-020-01598-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-020-01598-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T23:10:14Z","timestamp":1697497814000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-020-01598-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,6]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1598"],"URL":"https:\/\/doi.org\/10.1186\/s12931-020-01598-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-50645\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-50645\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-50645\/v1","asserted-by":"object"}]},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,6]]},"assertion":[{"value":"29 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experiments involving animals were performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care Committee (IACUC), which is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International, China and Experimental Animal Committee of the Hunan University of Chinese Medicine (License Numbers: XMBH-201910080005).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}