{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:39:39Z","timestamp":1777901979993,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":["Science Progress"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hirschsprung's disease (HSCR) is a rare congenital disorder attributed to the defects of enteric neural crest cells. We aim to identify characteristic phosphorylation proteins and preliminarily explore underlying related action mechanisms in HSCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Colon samples from HSCR patients underwent proteomic and phosphoproteomic sequencing to identify differentially expressed phosphoproteins (DEPPs) and proteins (DEPs). Interaction network construction and analysis of correlations with upstream phosphorylating kinases were employed to pinpoint core proteins. HSCR rat models were established through enema administration of Benzalkonium chloride and evaluated by measuring colon cross-sectional area, colon weight, AchE, and PGP9.5 levels. Histopathological damage was assessed via hematoxylin and eosin staining. Protein expression was analyzed using western blotting. Furthermore, the impact of SRC kinase in HSCR was investigated utilizing an SRC-specific inhibitor in HSCR rat models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 5725 DEPPs were identified, with SRC kinase emerging as a key regulatory protein. In the HSCR rat model, SRC expression was elevated along with increased pCAV1 and FLNA levels. Notably, inhibition of SRC protein kinase activity by 1-(tert-butyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d] pyrimidin-4-amine (PP2) led to reduced colon cross-sectional area and weight, an increase in the number of colonic ganglion cells, heightened AchE levels, enhanced PGP9.5 expression, and slight enlargement of the crypt, thereby alleviating HSCR symptoms in rats. Additionally, SRC kinase inhibition following PP2 treatment decreased the expression of pCAV1 and FLNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of SRC kinase activity may potentially reduce CAV1\/FLNA expression, ultimately alleviating the severity of HSCR in rats.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/00368504251336287","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T03:07:32Z","timestamp":1745896052000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Suppression of SRC protein kinase activity alleviates the severity of aganglionosis by impairing CAV1\/FLNA expression"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8418-8794","authenticated-orcid":false,"given":"Xiaogang","family":"Xu","sequence":"first","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"},{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglong","family":"Lan","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Xia","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"},{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jixiao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"e_1_3_4_2_2","article-title":"Hirschsprung's disease \u2013 recent understanding of embryonic aspects, etiopathogenesis and future treatment avenues","volume":"56","author":"Klein M","year":"2020","unstructured":"Klein M, Varga I. Hirschsprung's disease \u2013 recent understanding of embryonic aspects, etiopathogenesis and future treatment avenues. Medicina (Kaunas) 2020; 56: 611.","journal-title":"Medicina (Kaunas)"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37928-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00268-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00465-y"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2016.11.023"},{"key":"e_1_3_4_7_2","first-page":"1319","article-title":"Hirschsprung's disease: diagnosis and management","volume":"74","author":"Kessmann J","year":"2006","unstructured":"Kessmann J. Hirschsprung's disease: diagnosis and management. Am Fam Physician 2006; 74: 1319\u20131322.","journal-title":"Am Fam Physician"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082675"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12070984"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E20-01-0084"},{"key":"e_1_3_4_11_2","article-title":"WISP1 induces the expression of macrophage migration inhibitory factor (MIF) in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways","author":"Christopoulou ME","unstructured":"Christopoulou ME, et al. WISP1 induces the expression of macrophage migration inhibitory factor (MIF) in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways. Am J Physiol Cell Physiol 2023; 326: C850\u2013C865.","journal-title":"Am J Physiol Cell Physiol"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900325R"},{"key":"e_1_3_4_13_2","first-page":"36","article-title":"Simultaneous inhibition of c-Abl and Src kinases abrogates the exaggerated expression of profibrotic genes in cultured systemic sclerosis dermal fibroblasts","volume":"36","author":"Piera-Velazquez S.","year":"2018","unstructured":"Piera-Velazquez S., Jimenez S.A., Simultaneous inhibition of c-Abl and Src kinases abrogates the exaggerated expression of profibrotic genes in cultured systemic sclerosis dermal fibroblasts. Clin Exp Rheumatol, 2018. 36 : p. 36\u201344.","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/bio.058904"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00383.2010"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1044834"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1237456"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.080804"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e18653"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.04.009"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-023-01645-5"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-019-04505-1"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.1038343"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126555"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac199"},{"key":"e_1_3_4_26_2","unstructured":"National Research Council Division on Earth and Life Studies Institute for Laboratory Animal Research Committee for the Update of the Guide for the Care and Use of Laboratory Animals Guide for the Care and Use of Laboratory Animals. Publication 2011. Vol. 327. pp. 963\u2013965."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/58\/5\/1549"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2020.088"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09892-9"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.06.004"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0718-x"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13615"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.03.024"},{"key":"e_1_3_4_35_2","article-title":"Proteomic analysis provides a new sight into the CRABP1 expression in the pathogenesis of Hirschsprung disease","author":"Bu L","unstructured":"Bu L, Wang X, Du G, et al. Proteomic analysis provides a new sight into the CRABP1 expression in the pathogenesis of Hirschsprung disease. Biochem Genet. Epub ahead of print 2024. DOI: 10.1007\/s10528-024-10913-3.","journal-title":"Biochem Genet."},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.33"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA120.002325"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.184"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3182a934c7"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2019.01.001"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.02.025"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0741"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-019-1147-7"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-014-0081-7"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0420-2"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.04.001"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612023393323"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00141.2017"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05299-x"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12282-7"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22083831"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200701006"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00003.2014"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2022.106236"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.044476"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.02.048"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.7.3025-3035.2004"}],"container-title":["Science Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00368504251336287","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00368504251336287","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00368504251336287","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:15:45Z","timestamp":1777634145000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00368504251336287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1177\/00368504251336287"],"URL":"https:\/\/doi.org\/10.1177\/00368504251336287","relation":{},"ISSN":["0036-8504","2047-7163"],"issn-type":[{"value":"0036-8504","type":"print"},{"value":"2047-7163","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"article-number":"00368504251336287"}}