{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:13:19Z","timestamp":1790172799272,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2018,12]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Release of 5\u2010hydroxytryptamine (5\u2010HT<\/jats:styled-content>; serotonin) from activated platelets following microvascular injury leads to tissue fibrosis. 5\u2010HT<\/jats:styled-content> strongly induces extracellular matrix synthesis in dermal fibroblasts in a transforming growth factor beta 1 (TGF<\/jats:styled-content>\u2010\u03b21)\u2010dependent manner.<\/jats:p><\/jats:sec>Aim<\/jats:title>To evaluate anti\u2010fibrotic properties of inhibitors of 5\u2010HT<\/jats:styled-content>2<\/jats:sub> and 5\u2010HT<\/jats:styled-content>2B<\/jats:sub> (terguride, SB<\/jats:styled-content>204741) respectively in human adult dermal fibroblasts (HADF<\/jats:styled-content>) derived from a patient with scleroderma.<\/jats:p><\/jats:sec>Methods<\/jats:title>Anti\u2010fibrotic efficacy of 5\u2010HT<\/jats:styled-content>2<\/jats:sub> and 5\u2010HT<\/jats:styled-content>2B<\/jats:sub> inhibitors was evaluated as per two strategies: HADF<\/jats:styled-content> were incubated with 5\u2010HT<\/jats:styled-content> (1\u00a0\u03bcM)\/TGF<\/jats:styled-content>\u2010\u03b21 (10\u00a0ng\/mL<\/jats:styled-content>) for 1\u00a0hour followed by 5\u2010HT<\/jats:styled-content> (1\u00a0\u03bcM)\/TGF<\/jats:styled-content>\u2010\u03b21 (10\u00a0ng\/mL<\/jats:styled-content>) and terguride or SB<\/jats:styled-content>204741 (1\u00a0\u03bcM, each) for 24\u00a0hours (post\u2010treatment strategy) and HADF<\/jats:styled-content> were treated with terguride or SB<\/jats:styled-content>204741 (1\u00a0\u03bcM, each) for 1\u00a0hour followed by 5\u2010HT<\/jats:styled-content> (1\u00a0\u03bcM)\/TGF<\/jats:styled-content>\u2010\u03b21 (10\u00a0ng\/mL<\/jats:styled-content>) for 24\u00a0hours (pre\u2010treatment strategy). Real time quantitative polymerase chain reaction for expression of pro\u2010fibrotic (TGF<\/jats:styled-content>\u03921<\/jats:italic>, COL<\/jats:styled-content>1A1<\/jats:italic>, COL<\/jats:styled-content>1A2<\/jats:italic>, ACTA<\/jats:styled-content>2<\/jats:italic>, CTGF<\/jats:styled-content><\/jats:italic> and FN<\/jats:styled-content>1<\/jats:italic>) and anti\u2010fibrotic genes (MMP<\/jats:styled-content>2<\/jats:italic>\/TIMP<\/jats:styled-content>1<\/jats:italic>) was performed. Expression of type I collagen, alpha smooth muscle actin (\u03b1\u2010SMA<\/jats:styled-content>), phosphorylation of Smad3, ERK<\/jats:styled-content>1\/2 and STAT<\/jats:styled-content>3 was examined by immunoblotting.<\/jats:p><\/jats:sec>Results<\/jats:title>Stimulation of HADF cells with 5\u2010HT<\/jats:styled-content>\/TGF<\/jats:styled-content>\u2010\u03b21 led to the increased expression of pro\u2010fibrotic genes which was significantly reduced by both terguride and SB<\/jats:styled-content>204741. Expression of anti\u2010fibrotic genes was not affected upon incubation with the inhibitors. In 5\u2010HT<\/jats:styled-content>\u2010stimulated HADF<\/jats:styled-content>, treatment with terguride and SB<\/jats:styled-content>204741 decreased type I collagen and \u03b1\u2010SMA<\/jats:styled-content>. In 5\u2010HT<\/jats:styled-content>\/TGF<\/jats:styled-content>\u2010\u03b21 stimulated HADF<\/jats:styled-content>, terguride and SB<\/jats:styled-content>204741 treatment reduced ERK<\/jats:styled-content>1\/2 and STAT<\/jats:styled-content>3 phosphorylation but did not influence Smad3 phosphorylation.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Terguride and SB<\/jats:styled-content>204741 reduce pro\u2010fibrotic potential of HADF<\/jats:styled-content> cells and suppress TGF<\/jats:styled-content>\u2010\u03b21\u2010mediated non\u2010canonical pathways, ERK<\/jats:styled-content>1\/2 and STAT<\/jats:styled-content>3 which have been implicated in the regulation of pro\u2010fibrotic genes and in the development of fibrosis. Taken together, our data suggest that 5\u2010HT inhibitors might reduce fibrosis via suppression of TGF\u2010beta1\u2010mediated non\u2010canonical signaling pathways. These observations have important therapeutic implications for fibrotic disorders like scleroderma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13386","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T07:49:51Z","timestamp":1536738591000},"page":"2128-2138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["5\u2010HT<\/scp>2<\/sub> and 5\u2010HT<\/scp>2B<\/sub> antagonists attenuate pro\u2010fibrotic phenotype in human adult dermal fibroblasts by blocking TGF<\/scp>\u2010\u03b21 induced non\u2010canonical signaling pathways including STAT<\/scp>3 : implications for fibrotic diseases like scleroderma"],"prefix":"10.1111","volume":"21","author":[{"given":"Saurabh","family":"Chaturvedi","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-7396","authenticated-orcid":false,"given":"Durga Prasanna","family":"Misra","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Transplantation Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Hygia Institute of Pharmaceutical Education and Research Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshit","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit Kumar","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-1233","authenticated-orcid":false,"given":"Vikas","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0806188"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-0510"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31139"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2002.24.6.693065"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00061.2002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101629"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77958"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.591321"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890008998827"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:29:1:31"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1933740100"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6011"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702055"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200302-264OC"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00746-8"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.6.F922"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.134353"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050767"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.09.010"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2810"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00114.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.06.017"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.26"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23146"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23766.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01236-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1955.tb00102.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-97-23734"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.40507.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/wmts.50"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.06.012"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3851"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-10-0991"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.08.012"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1306-5"},{"key":"e_1_2_7_40_1","first-page":"189","article-title":"Therapy with terguride","volume":"33","author":"Werner K","year":"1989","journal-title":"Nichidoku\u2010Iho"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00126907"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1756-185X.13386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.13386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T23:30:26Z","timestamp":1694734226000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.13386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,12]]},"references-count":40,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1111\/1756-185X.13386"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.13386","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,12]]},"assertion":[{"value":"2018-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}