{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:58:30Z","timestamp":1778648310177,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP 1037304"],"award-info":[{"award-number":["APP 1037304"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We showed previously that the Schistosoma japonicum insulin-like peptide (SjILP) binds the worm insulin receptors, thereby, activating the parasite\u2019s insulin pathway and emphasizing its important role in regulating uptake of glucose, a nutrient essential for parasite survival. Here we show that SjILP is differentially expressed in the schistosome life cycle and is especially highly transcribed in eggs, miracidia, and adult female worms. RNA inference was employed to knockdown SjILP in adults in vitro, with suppression confirmed by significantly reduced protein production, declined adenosine diphosphate levels, and reduction in glucose consumption. Immunolocalization showed that SjILP is located to lateral gland cells of mature intra-ovular miracidia in the schistosome egg, and is distributed on the ciliated epithelium and internal cell masses of newly transformed miracidia. In schistosomula, SjILP is present on the tegument in two antero-lateral points, indicating highly polarized expression during cercarial transformation. Analysis of serum from S. japonicum-infected mice by ELISA using a recombinant form of SjILP as an antigen revealed IgG immunoreactivity to this molecule at 7 weeks post-infection indicating it is likely secreted from mature eggs into the host circulation. These findings provide further insights on ILP function in schistosomes and its essential roles in parasite survival and growth in different development stages.<\/jats:p>","DOI":"10.3390\/ijms20071565","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T03:38:52Z","timestamp":1553830732000},"page":"1565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gene Expression in Developmental Stages of Schistosoma japonicum Provides Further Insight into the Importance of the Schistosome Insulin-Like Peptide"],"prefix":"10.3390","volume":"20","author":[{"given":"Xiaofeng","family":"Du","sequence":"first","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm K.","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, The University of Queensland, Gatton 4343, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujeevi S. K.","family":"Nawaratna","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"},{"name":"School of Medicine, Griffith University, Gold Coast 4222, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiwanthi","family":"Ranasinghe","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunrong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4975-4615","authenticated-orcid":false,"given":"Pengfei","family":"Cai","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-1449","authenticated-orcid":false,"given":"Donald P.","family":"McManus","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"You","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1056\/NEJMra012396","article-title":"Schistosomiasis","volume":"346","author":"Ross","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"d2651","DOI":"10.1136\/bmj.d2651","article-title":"Diagnosis and management of schistosomiasis","volume":"342","author":"Gray","year":"2011","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.trsl.2013.03.006","article-title":"New vaccines for neglected parasitic diseases and dengue","volume":"162","author":"Beaumier","year":"2013","journal-title":"Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1085\/jgp.33.5.475","article-title":"Carbohydrate metabolism of schistosoma mansoni","volume":"33","author":"Bueding","year":"1950","journal-title":"J. Gen. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0020-7519(01)00348-4","article-title":"Transforming growth factor-beta and insulin-like signalling pathways in parasitic helminths","volume":"32","author":"Beall","year":"2002","journal-title":"Int. J. Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature08140","article-title":"The Schistosoma japonicum genome reveals features of host-parasite interplay","volume":"460","author":"Zhou","year":"2009","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature08160","article-title":"The genome of the blood fluke Schistosoma mansoni","volume":"460","author":"Berriman","year":"2009","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17759","DOI":"10.1038\/srep17759","article-title":"Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets","volume":"5","author":"Stroehlein","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng.1065","article-title":"Whole-genome sequence of Schistosoma haematobium","volume":"44","author":"Young","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13071-017-2095-7","article-title":"Identification and functional characterisation of a Schistosoma japonicum insulin-like peptide","volume":"10","author":"Du","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1742-4658.2006.05610.x","article-title":"Diversification of the insulin receptor family in the helminth parasite Schistosoma mansoni","volume":"274","author":"Khayath","year":"2007","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"You, H., Zhang, W., Jones, M.K., Gobert, G.N., Mulvenna, J., Rees, G., Spanevello, M., Blair, D., Duke, M., and Brehm, K. (2010). Cloning and characterisation of Schistosoma japonicum insulin receptors. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009868"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"You, H., Gobert, G.N., Cai, P., Mou, R., Nawaratna, S., Fang, G., Villinger, F., and McManus, D.P. (2015). Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003730"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.ijpara.2009.06.006","article-title":"Transcriptional profiles of adult male and female Schistosoma japonicum in response to insulin reveal increased expression of genes involved in growth and development","volume":"39","author":"You","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vanderstraete, M., Gouignard, N., Cailliau, K., Morel, M., Lancelot, J., Bodart, J.F., and Dissous, C. (2013). Dual targeting of insulin and venus kinase Receptors of Schistosoma mansoni for novel anti-schistosome therapy. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002226"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/febs.12655","article-title":"Identification of putative insulin-like peptides and components of insulin signaling pathways in parasitic platyhelminths by the use of genome-wide screening","volume":"281","author":"Wang","year":"2014","journal-title":"FEBS J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.ijpara.2012.06.002","article-title":"The insulin receptor is a transmission blocking veterinary vaccine target for zoonotic Schistosoma japonicum","volume":"42","author":"You","year":"2012","journal-title":"Int. J. Parasitol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s13071-016-1615-1","article-title":"Functional characterisation of Schistosoma japonicum acetylcholinesterase","volume":"9","author":"You","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s11302-014-9416-5","article-title":"Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP","volume":"10","author":"Bhardwaj","year":"2014","journal-title":"Purinergic Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.molbiopara.2011.12.007","article-title":"Genome-wide identification and characterization of a panel of house-keeping genes in Schistosoma japonicum","volume":"182","author":"Liu","year":"2012","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Herbert, M., Coppieters, N., Lasham, A., Cao, H., and Reid, G. (2011). The importance of RT-qPCR primer design for the detection of siRNA-mediated mRNA silencing. BMC Res. Notes, 4.","DOI":"10.1186\/1756-0500-4-148"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Melville, S.E. (2004). Parasite Genomics Protocols, Humana Press.","DOI":"10.1385\/1592597939"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.molbiopara.2011.01.007","article-title":"Quantitative retrotransposon anchored PCR confirms transduction efficiency of transgenes in adult Schistosoma mansoni","volume":"177","author":"Rinaldi","year":"2011","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s001250050349","article-title":"Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms","volume":"38","author":"Kotzke","year":"1995","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1006\/expr.1995.1152","article-title":"Schistosoma: Rate of glucose import is altered by acetylcholine interaction with tegumental acetylcholine receptors and acetylcholinesterase","volume":"81","author":"Camacho","year":"1995","journal-title":"Exp. Parasitol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"You, H., Liu, C., Du, X., Nawaratna, S., Rivera, V., Harvie, M., Jones, M., and McManus, D.P. (2018). Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082426"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1645\/GE-3402.1","article-title":"Host glucose metabolism mediates T4 and IL-7 action on Schistosoma mansoni development","volume":"91","author":"Saule","year":"2005","journal-title":"J. Parasitol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0014-4894(81)90096-5","article-title":"Schistosoma mansoni: Effect of insulin and a low-molecular-weight fraction of serum on schistosomula in chemically defined media","volume":"52","author":"Smolarsky","year":"1981","journal-title":"Exp. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00427-009-0285-9","article-title":"The embryonic development of Schistosoma mansoni eggs: Proposal for a new staging system","volume":"219","author":"Jurberg","year":"2009","journal-title":"Dev. Genes Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1051\/parasite\/2000074297","article-title":"Study of the distribution pattern of Schistosoma haematobium egg antigens recognised by six different monoclonal antibodies in the parasite and the host","volume":"7","author":"Royers","year":"2000","journal-title":"Parasite"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1017\/S0031182001007351","article-title":"The schistosome egg: Development and secretions","volume":"122","author":"Ashton","year":"2001","journal-title":"Parasitology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.ijpara.2009.04.002","article-title":"Protein kinase C signalling during miracidium to mother sporocyst development in the helminth parasite, Schistosoma mansoni","volume":"39","author":"Ludtmann","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"ref_33","unstructured":"Jamieson, B.G.M. (2016). Schistosoma: Biology, Pathology and Control, Taylor & Francis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129","DOI":"10.7883\/yoken1952.49.129","article-title":"Schistosoma mansoni: The ultrastructure of larval morphogenesis in Biomphalaria glabrata and of associated host-parasite interactions","volume":"49","author":"Pan","year":"1996","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.molbiopara.2008.11.005","article-title":"Proteomic analysis of Schistosoma mansoni proteins released during in vitro miracidium-to-sporocyst transformation","volume":"164","author":"Wu","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"541268","DOI":"10.1155\/2012\/541268","article-title":"Schistosoma tegument proteins in vaccine and diagnosis development: An update","volume":"2012","author":"Fonseca","year":"2012","journal-title":"J. Parasitol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gobert, G.N., Moertel, L., Brindley, P.J., and McManus, D.P. (2009). Developmental gene expression profiles of the human pathogen Schistosoma japonicum. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-128"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0165-022X(84)90040-X","article-title":"Electroblotting of multiple gels: A simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose","volume":"10","year":"1984","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"You, H., McManus, D.P., Hu, W., Smout, M.J., Brindley, P.J., and Gobert, G.N. (2013). Transcriptional responses of in vivo praziquantel exposure in schistosomes identifies a functional role for calcium signalling pathway member CamKII. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003254"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.molbiopara.2007.10.009","article-title":"RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade","volume":"157","author":"Morales","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.molbiopara.2009.05.002","article-title":"RNA interference targeting leucine aminopeptidase blocks hatching of Schistosoma mansoni eggs","volume":"167","author":"Rinaldi","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0166-6851(93)90042-V","article-title":"Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni","volume":"58","author":"Vasconcelos","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.1074\/jbc.M113.531558","article-title":"Solution structure, membrane interactions, and protein binding partners of the tetraspanin Sm-TSP-2, a vaccine antigen from the human blood fluke Schistosoma mansoni","volume":"289","author":"Jia","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1017\/S0031182015001328","article-title":"A novel coagulation inhibitor from Schistosoma japonicum","volume":"142","author":"Ranasinghe","year":"2015","journal-title":"Parasitology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/infdis\/jiv464","article-title":"Sensory Protein Kinase Signaling in Schistosoma mansoni Cercariae: Host Location and Invasion","volume":"212","author":"Ressurreicao","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ijpara.2009.10.014","article-title":"A comparative proteomic study of the undeveloped and developed Schistosoma mansoni egg and its contents: The miracidium, hatch fluid and secretions","volume":"40","author":"Mathieson","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1017\/S0031182097001091","article-title":"A method for the isolation of schistosome eggs and miracidia free of contaminating host tissues","volume":"115","author":"Dalton","year":"1997","journal-title":"Parasitology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Milligan, J.N., and Jolly, E.R. (2011). Cercarial transformation and in vitro cultivation of Schistosoma mansoni schistosomules. J. Vis. Exp.","DOI":"10.3791\/3191-v"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2307\/3280632","article-title":"Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing","volume":"67","author":"Basch","year":"1981","journal-title":"J. Parasitol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1565\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:41:17Z","timestamp":1760186477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijms20071565"],"URL":"https:\/\/doi.org\/10.3390\/ijms20071565","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,28]]}}}