{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:50:03Z","timestamp":1775019003033,"version":"3.50.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"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":["31372427"],"award-info":[{"award-number":["31372427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Vet Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endoplasmic reticulum stress (ERS) and oxidative stress (OS) are adaptive responses of the body to stressor stimulation. Although it has been verified that <jats:italic>Trichinella spiralis<\/jats:italic> (<jats:italic>T. spiralis<\/jats:italic>) can induce ERS and OS in the host, their association is still unclear. Therefore, this study explored whether <jats:italic>T. spiralis<\/jats:italic>-secreted serpin-type serine protease inhibitor (TsAdSPI) is involved in regulating the relationship between ERS and OS in the host intestine. In this study, mice jejunum and porcine\u00a0small intestinal epithelial cells (IECs) were detected using qPCR, western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and detection kits. The results showed that ERS- and OS-related indexes changed significantly after TsAdSPI stimulation, and Bip was located in IECs, indicating that TsAdSPI could induce ERS and OS in IECs. After the use of an ERS inhibitor, OS-related indexes were inhibited, suggesting that TsAdSPI-induced OS depends on ERS. When the three ERS signalling pathways, ATF6, IRE1, and PERK, were sequentially suppressed, OS was only regulated by the PERK pathway, and the PERK-eif2\u03b1-CHOP-ERO1\u03b1 axis played a key role. Similarly, the expression of ERS-related indexes and the level of intracellular Ca<jats:sup>2+<\/jats:sup> were inhibited after adding the OS inhibitor, and the expression of ERS-related indexes decreased significantly after inhibiting calcium transfer. This finding indicated that TsAdSPI-induced OS could affect ERS by promoting Ca<jats:sup>2+<\/jats:sup> efflux from the endoplasmic reticulum. The detection of the ERS and OS sequences revealed that OS occurred before ERS. Finally, changes in apoptosis-related indexes were detected, and the results indicated that TsAdSPI-induced ERS and OS could regulate IEC apoptosis. In conclusion, TsAdSPI induced OS after entering IECs, OS promoted ERS by enhancing Ca<jats:sup>2+<\/jats:sup> efflux, and ERS subsequently strengthened OS by activating the PERK-eif2\u03b1-CHOP-ERO1\u03b1 axis. ERS and OS induced by TsAdSPI synergistically promoted IEC apoptosis. This study provides a foundation for exploring the invasion mechanism of <jats:italic>T. spiralis<\/jats:italic> and the pathogenesis of host intestinal dysfunction after invasion.<\/jats:p>","DOI":"10.1186\/s13567-024-01334-6","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:02:39Z","timestamp":1718373759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Regulatory effects of Trichinella spiralis serpin-type serine protease inhibitor on endoplasmic reticulum stress and oxidative stress in host intestinal epithelial cells"],"prefix":"10.1186","volume":"55","author":[{"given":"Jingbo","family":"Zhen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiankun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junchen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8410-5587","authenticated-orcid":false,"given":"Yixin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caixia","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"1334_CR1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00103-23","volume":"91","author":"JB Zhen","year":"2023","unstructured":"Zhen JB, Wang RB, Zhang YH, Sun F, Lin LH, Li ZX, Han Y, Lu YX (2023) Effects of Trichinella spiralis and its serine protease inhibitors on autophagy of host small intestinal cells. Infect Immun 91:e0010323","journal-title":"Infect Immun"},{"key":"1334_CR2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13567-023-01258-7","volume":"55","author":"YD Liu","year":"2024","unstructured":"Liu YD, Liu JC, Wang N, You XH, Yang YM, Ding J, Liu XL, Liu MY, Li C, Xu N (2024) Quantitative label-free proteomic analysis of excretory-secretory proteins in different developmental stages of Trichinella spiralis. Vet Res 55:4","journal-title":"Vet Res"},{"key":"1334_CR3","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13567-022-01036-x","volume":"53","author":"JY Xu","year":"2022","unstructured":"Xu JY, Pang ZX, Zhang JP, Xia S, Wang RB, Zhang YH, Zhen JB, Song XW, Lin LH, Sun F, Xuan XX, Lu YX (2022) Regulatory effects of Trichinella spiralis and a serine protease inhibitor on the endoplasmic reticulum stress response of intestinal epithelial cells. Vet Res 53:18","journal-title":"Vet Res"},{"key":"1334_CR4","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1017\/S0031182011002435","volume":"139","author":"AJ Molehin","year":"2012","unstructured":"Molehin AJ, Gobert GN, McManus DP (2012) Serine protease inhibitors of parasitic helminths. Parasitology 139:681\u2013695","journal-title":"Parasitology"},{"key":"1334_CR5","doi-asserted-by":"publisher","first-page":"17045","DOI":"10.1038\/s41598-019-52624-5","volume":"9","author":"JY Xu","year":"2019","unstructured":"Xu JY, Yu PC, Wu LJ, Liu MX, Lu YX (2019) Regulatory effect of two Trichinella spiralis serine protease inhibitors on the host\u2019s immune system. Sci Rep 9:17045","journal-title":"Sci Rep"},{"key":"1334_CR6","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3390\/v8050124","volume":"8","author":"SL Cervantes-Ortiz","year":"2016","unstructured":"Cervantes-Ortiz SL, Cuervo NZ, Grandvaux N (2016) Respiratory syncytial virus and cellular stress responses: impact on replication and physiopathology. Viruses 8:124","journal-title":"Viruses"},{"key":"1334_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2022.109548","volume":"273","author":"YS Zhou","year":"2022","unstructured":"Zhou YS, Zhou XJ, Dong WY, Zhang YX, Du J, Zhou XD, Fang WH, Wang XD, Song HH (2022) Porcine circovirus type 2 induces CHOP-ERO1\u03b1-ROS-mediated apoptosis in PK-15 cells. Vet Microbiol 273:109548","journal-title":"Vet Microbiol"},{"key":"1334_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virusres.2018.12.013","volume":"263","author":"WA R\u00edos-Ocampo","year":"2019","unstructured":"R\u00edos-Ocampo WA, Navas MC, Faber KN, Daemen T, Moshage H (2019) The cellular stress response in hepatitis C virus infection: A balancing act to promote viral persistence and host cell survival. Virus Res 263:1\u20138","journal-title":"Virus Res"},{"key":"1334_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molbiopara.2014.09.002","volume":"197","author":"S Dolai","year":"2014","unstructured":"Dolai S, Adak S (2014) Endoplasmic reticulum stress responses in Leishmania. Mol Biochem Parasitol 197:1\u20138","journal-title":"Mol Biochem Parasitol"},{"key":"1334_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.670874","volume":"12","author":"M Peng","year":"2021","unstructured":"Peng M, Chen F, Wu ZD, Shen J (2021) Endoplasmic reticulum stress, a target for drug design and drug resistance in parasitosis. Front Microbiol 12:670874","journal-title":"Front Microbiol"},{"key":"1334_CR11","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1017\/S0031182009991351","volume":"137","author":"S Chandramathi","year":"2010","unstructured":"Chandramathi S, Suresh K, Shuba S, Mahmood A, Kuppusamy UR (2010) High levels of oxidative stress in rats infected with Blastocystis hominis. Parasitology 137:605\u2013611","journal-title":"Parasitology"},{"key":"1334_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exppara.2014.06.017","volume":"145","author":"YR Yu","year":"2014","unstructured":"Yu YR, Deng MJ, Lu WW, Zhang JS, Jia MZ, Huang J, Qi YF (2014) Endoplasmic reticulum stress-mediated apoptosis is activated in intestines of mice with Trichinella spiralis infection. Exp Parasitol 145:1\u20136","journal-title":"Exp Parasitol"},{"key":"1334_CR13","doi-asserted-by":"publisher","DOI":"10.1017\/S0022149X20000206","volume":"94","author":"DI Elgendy","year":"2020","unstructured":"Elgendy DI, Othman AA, Saad MAH, Soliman NA, Mwafy SE (2020) Resveratrol reduces oxidative damage and inflammation in mice infected with Trichinella spiralis. J Helminthol 94:e140","journal-title":"J Helminthol"},{"key":"1334_CR14","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3390\/antiox10060872","volume":"10","author":"J Lee","year":"2021","unstructured":"Lee J, Song CH (2021) Effect of reactive oxygen species on the endoplasmic reticulum and mitochondria during intracellular pathogen infection of mammalian cells. Antioxidants 10:872","journal-title":"Antioxidants"},{"key":"1334_CR15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.tim.2005.02.004","volume":"13","author":"KD Tardif","year":"2005","unstructured":"Tardif KD, Waris G, Siddiqui A (2005) Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol 13:159\u2013163","journal-title":"Trends Microbiol"},{"key":"1334_CR16","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1097\/MIB.0000000000000238","volume":"21","author":"SS Cao","year":"2015","unstructured":"Cao SS (2015) Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel disease. Inflamm Bowel Dis 21:636\u2013644","journal-title":"Inflamm Bowel Dis"},{"key":"1334_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2023.110011","volume":"322","author":"SM Razavi","year":"2023","unstructured":"Razavi SM, Soltan MS, Abbasian K, Karami A, Nazifi S (2023) Host oxidative stress in piroplasmosis: a review in domestic animals. Vet Parasitol 322:110011","journal-title":"Vet Parasitol"},{"key":"1334_CR18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1179\/174329210X12650506623203","volume":"15","author":"LY Chung","year":"2010","unstructured":"Chung LY, Wang LC, Chen CH, Lin HY, Yen CM (2010) Kinetic change of oxidative stress in cerebrospinal fluid of mice infected with Angiostrongylus cantonensis. Redox Rep 15:43\u201348","journal-title":"Redox Rep"},{"key":"1334_CR19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13567-023-01139-z","volume":"54","author":"YS Zhou","year":"2023","unstructured":"Zhou YS, Zhang YX, Dong WY, Gan SQ, Du J, Zhou XD, Wang WH, Wang XD, Song HH (2023) Porcine epidemic diarrhea virus activates PERK-ROS axis to benefit its replication in Vero E6 cells. Vet Res 54:9","journal-title":"Vet Res"},{"key":"1334_CR20","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3390\/ijms17030327","volume":"17","author":"HMA Zeeshan","year":"2016","unstructured":"Zeeshan HMA, Lee GH, Kim HR, Chae HJ (2016) Endoplasmic reticulum stress and associated ROS. Int J Mol Sci 17:327","journal-title":"Int J Mol Sci"},{"key":"1334_CR21","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3892\/or.2021.7933","volume":"45","author":"XJ Fu","year":"2021","unstructured":"Fu XJ, Cui JJ, Meng XJ, Jiang PY, Zheng QL, Zhao WW, Chen XH (2021) Endoplasmic reticulum stress, cell death and tumor: association between endoplasmic reticulum stress and the apoptosis pathway in tumors. Oncol Rep 45:801\u2013808","journal-title":"Oncol Rep"},{"key":"1334_CR22","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s00204-013-1034-4","volume":"87","author":"K Sinha","year":"2013","unstructured":"Sinha K, Das J, Pal PB, Sil PC (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 87:1157\u20131180","journal-title":"Arch Toxicol"},{"key":"1334_CR23","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1096\/fj.05-5338fje","volume":"20","author":"M Guha","year":"2006","unstructured":"Guha M, Kumar S, Choubey V, Maity P, Bandyopadhyay U (2006) Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J 20:1224","journal-title":"FASEB J"}],"container-title":["Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-024-01334-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13567-024-01334-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13567-024-01334-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:02:42Z","timestamp":1718373762000},"score":1,"resource":{"primary":{"URL":"https:\/\/veterinaryresearch.biomedcentral.com\/articles\/10.1186\/s13567-024-01334-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,14]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1334"],"URL":"https:\/\/doi.org\/10.1186\/s13567-024-01334-6","relation":{},"ISSN":["1297-9716"],"issn-type":[{"value":"1297-9716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,14]]},"assertion":[{"value":"12 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The feeding and experimental procedures for the mice were carried out in accordance with the Chinese Animal Management Ordinance. The animal experiment standards were approved by the Animal Management Committee of Northeast Agricultural University and implemented in accordance with animal ethics guidelines and approved protocols (Animal Ethics Committee approval number SYXK [Hei] 2016-007).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}