{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:44:40Z","timestamp":1790689480663,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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":["32172861"],"award-info":[{"award-number":["32172861"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2021-MS-221"],"award-info":[{"award-number":["2021-MS-221"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Liaoning Provincial Department of Education","award":["LSNJC201917"],"award-info":[{"award-number":["LSNJC201917"]}]},{"name":"Zoonosis Research Engineering Laboratory Project of Liaoning Province","award":["01072917001"],"award-info":[{"award-number":["01072917001"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role in the pathogenic process of G. parasuis. Long non-coding RNA maternally expressed gene 3 (MEG3) is associated with G. parasuis infection, but its mechanism remains incompletely unclear. This study aimed to investigate the role of MEG3 in G. parasuis-induced apoptosis of the porcine alveolar macrophage cell line 3D4\/21 and its detailed molecular mechanism. Here, we found that MEG3 overexpression promoted G. parasuis-induced apoptosis and upregulated key extrinsic pathway proteins caspase-8 (CASP8) and caspase-3 (CASP3). Mechanistically, MEG3 functioned as a competing endogenous RNA by sponging ssc-miR-135, which directly targets and inhibits CASP8. Consequently, MEG3 overexpression alleviated ssc-miR-135-mediated repression of CASP8. Functional rescue experiments confirmed that either ssc-miR-135 mimic or CASP8 siRNA reversed the pro-apoptotic effect of MEG3. In conclusion, this study reveals that MEG3 relieves the inhibitory effect of ssc-miR-135 on CASP8 through competitively binding, thereby regulating G. parasuis-induced apoptosis of 3D4\/21 cells. This study provides new insights into the pathogenic molecular mechanism of G. parasuis.<\/jats:p>","DOI":"10.3390\/microorganisms13102287","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:37:21Z","timestamp":1759311441000},"page":"2287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["LncRNA MEG3 Regulates Glaesserella parasuis-Induced Apoptosis of Porcine Alveolar Macrophages via Regulating ssc-miR-135\/CASP8 Axis"],"prefix":"10.3390","volume":"13","author":[{"given":"Yongchao","family":"Jia","sequence":"first","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Qian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlu","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronglan","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aobo","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanhua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-2273","authenticated-orcid":false,"given":"Yuanyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xu, J., Jin, X., Li, X., and Yang, D. (2025). Epidemiology and pathogenicity of Haemophilus parasuis in eastern China. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1589975"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Guo, Z., Zhou, Y., Li, N., Shen, A., Jia, Y., Yin, R., Yang, J., Yuan, J., and Yin, R. (2025). The Molecular Mechanism by Which miR-129a-3p Targets the TLR4\/NF-\u03baB Signaling Pathway to Regulate Inflammatory Damage in 3D4\/21 Cells Infected with Glaesserella parasuis. Animals, 15.","DOI":"10.3390\/ani15101355"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nielsen, D.W., Sarlo Davila, K.M., Brockmeier, S.L., and Hau, S.J. (2025). Transcriptional profile of Glaesserella parasuis in swine serosal and joint fluids. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1452973"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dai, L., Wan, J., Zhang, R., Xie, T., Jia, Y., Lu, Z., Zhang, F., Ke, W., Liu, F., and Lei, L. (2025). Multi-epitope vaccines Xlc and Ddc against Glaesserella parasuis infection in mice. Vet. Microbiol., 304.","DOI":"10.1016\/j.vetmic.2025.110491"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fu, S., Liu, H., Xu, L., Qiu, Y., Liu, Y., Wu, Z., Ye, C., Hou, Y., and Hu, C.A. (2018). Baicalin modulates NF-\u03baB and NLRP3 inflammasome signaling in porcine aortic vascular endothelial cells Infected by Haemophilus parasuis Causing Gl\u00e4sser\u2019s disease. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19293-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.rvsc.2023.03.021","article-title":"Virulence assessment of four Glaesserella parasuis strains isolated in Liaoning province of China","volume":"158","author":"Yan","year":"2023","journal-title":"Res. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, G., Niu, H., Zhang, Y., Li, Y., Xie, F., Langford, P.R., Liu, S., and Wang, C. (2017). Haemophilus parasuis cytolethal distending toxin induces cell cycle arrest and p53-dependent apoptosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177199"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13567-025-01580-2","article-title":"Glaesserella parasuis infection triggers endoplasmic reticulum stress-mediated pyroptosis via PERK\/eIF2\u03b1\/ATF4 axis and metabolic reprogramming in porcine alveolar macrophages","volume":"56","author":"Feng","year":"2025","journal-title":"Vet. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107141","DOI":"10.1016\/j.intimp.2020.107141","article-title":"LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p","volume":"90","author":"Meng","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41419-018-0350-2","article-title":"CASC2\/miR-24\/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8\/caspase-3","volume":"9","author":"Jin","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e23772","DOI":"10.1096\/fj.202302475RRR","article-title":"THUMPD3-AS1 inhibits ovarian cancer cell apoptosis through the miR-320d\/ARF1 axis","volume":"38","author":"Mu","year":"2024","journal-title":"FASEB J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Shi, S., Li, J., and Costa, M. (2023). Long Non-Coding RNA MEG3 in Metal Carcinogenesis. Toxics, 11.","DOI":"10.3390\/toxics11020157"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, J., Liu, W., Peng, F., Cao, X., Xie, X., and Peng, C. (2023). The multifaceted biology of lncR-Meg3 in cardio-cerebrovascular diseases. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1132884"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10571-021-01176-2","article-title":"The Mechanism Underlying the Regulation of Long Non-coding RNA MEG3 in Cerebral Ischemic Stroke","volume":"43","author":"Zhao","year":"2023","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Z., Gao, J., Sun, D., Jiao, Q., Ma, J., Cui, W., Lou, Y., Xu, F., Li, S., and Li, H. (2022). LncRNA MEG3: Potential stock for precision treatment of cardiovascular diseases. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1045501"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xu, J., Wang, X., Zhu, C., and Wang, K. (2022). A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.997633"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s43440-024-00661-x","article-title":"Long noncoding RNA MEG3: An active player in fibrosis","volume":"77","author":"Jiang","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104437","DOI":"10.1016\/j.drudis.2025.104437","article-title":"The multifaceted role of lncRNA MEG3 in kidney disease: A focus on mechanisms, therapeutic and diagnostic potential","volume":"30","author":"Puri","year":"2025","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jia, H.Y., Zhang, K., Lu, W.J., Xu, G.W., Zhang, J.F., and Tang, Z.L. (2019). LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21\/caspase-8. BMC Mol. Cell Biol., 20.","DOI":"10.1186\/s12860-019-0229-9"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1080\/21691401.2019.1623233","article-title":"Silence of MEG3 intensifies lipopolysaccharide-stimulated damage of human lung cells through modulating miR-4262","volume":"47","author":"Li","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1007\/s00284-021-02590-x","article-title":"LncRNA-MEG3 Regulates the Inflammatory Responses and Apoptosis in Porcine Alveolar Macrophages Infected with Haemophilus parasuis Through Modulating the miR-210\/TLR4 Axis","volume":"78","author":"Yin","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18361","DOI":"10.1002\/jcp.28469","article-title":"LncRNA-MEG3 promotes bovine myoblast differentiation by sponging miR-135","volume":"234","author":"Liu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e0023124","DOI":"10.1128\/msphere.00231-24","article-title":"Genomic insight into the diversity of Glaesserella parasuis isolates from 19 countries","volume":"9","author":"Gong","year":"2024","journal-title":"mSphere"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105617","DOI":"10.1016\/j.micpath.2022.105617","article-title":"Transcriptomics analysis reveals key lncRNAs and genes related to the infection of porcine lung macrophages by Glaesserella parasuis","volume":"169","author":"Zhou","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Liang, Y., Tan, X., and Liu, L. (2024). Host long noncoding RNAs in bacterial infections. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1419782"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aznaourova, M., Schmerer, N., Schmeck, B., and Schulte, L.N. (2020). Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.527484"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, B., Liu, X., Li, C., and Yang, N. (2024). LncRNA (BCO1-AS) regulate inflammatory responses in bacterial infection through caspase-1 in turbot (Scophthalmus maximus). Int. J. Biol. Macromol., 279.","DOI":"10.1016\/j.ijbiomac.2024.135131"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116456","DOI":"10.1016\/j.ecoenv.2024.116456","article-title":"Long non-coding RNA (CMR) involved in autoprotection in S. aureus mastitis in dairy cows by regulating miR-877\/FOXM1","volume":"278","author":"Chu","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/biof.1806","article-title":"Exosomal lnc-AFTR as a novel translation regulator of FAS ameliorates Staphylococcus aureus-induced mastitis","volume":"48","author":"Chen","year":"2022","journal-title":"Biofactors"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2287339","DOI":"10.1080\/21505594.2023.2287339","article-title":"LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells","volume":"14","author":"Mao","year":"2023","journal-title":"Virulence"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.vetmic.2011.12.002","article-title":"Cytolethal distending toxin (CDT) of the Haemophilus parasuis SC096 strain contributes to serum resistance and adherence to and invasion of PK-15 and PUVEC cells","volume":"157","author":"Zhang","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, J., Yan, P., Jia, Y., Guo, Z., Guo, Y., Yin, R., Wang, L., Fan, Z., Zhou, Y., and Yuan, J. (2024). Expression profiles of miRNAs in the lung tissue of piglets infected with Glaesserella parasuis and the roles of ssc-miR-135 and ssc-miR-155-3p in the regulation of inflammation. Comp. Immunol. Microbiol. Infect. Dis., 111.","DOI":"10.1016\/j.cimid.2024.102214"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, J.Y., Yang, Y., Ma, Y., Wang, F., Xue, A., Zhu, J., Yang, H., Chen, Q., Chen, M., and Ye, L. (2020). Potential regulatory role of lncRNA-miRNA-mRNA axis in osteosarcoma. Biomed. Pharmacother., 121.","DOI":"10.1016\/j.biopha.2019.109627"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s12079-023-00721-6","article-title":"miR-135 protects against atrial fibrillation by suppressing intracellular calcium-mediated NLRP3 inflammasome activation","volume":"17","author":"Yu","year":"2023","journal-title":"J. Cell Commun. Signal."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gupta, S., Lopez, M.A., Ektesabi, A.M., Tsoporis, J.N., Vaswani, C.M., Gandhi, S.Y., Fairn, G.D., Dos Santos, C.C., and Marshall, J.C. (2025). Caspase-8: Arbitrating Life and Death in the Innate Immune System. Cells, 14.","DOI":"10.3390\/cells14040240"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Samidurai, A., Olex, A.L., Ockaili, R., Kraskauskas, D., Roh, S.K., Kukreja, R.C., and Das, A. (2023). Integrated Analysis of lncRNA-miRNA-mRNA Regulatory Network in Rapamycin-Induced Cardioprotection against Ischemia\/Reperfusion Injury in Diabetic Rabbits. Cells, 12.","DOI":"10.3390\/cells12242820"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/10\/2287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:57:34Z","timestamp":1759312654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/10\/2287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["microorganisms13102287"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13102287","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}