{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:32:40Z","timestamp":1777944760910,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Jiangsu Youth Medical Talents Project","award":["QNRC2016874"],"award-info":[{"award-number":["QNRC2016874"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31400947"],"award-info":[{"award-number":["31400947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071234"],"award-info":[{"award-number":["82071234"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170836"],"award-info":[{"award-number":["82170836"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The clinical research center of neurological disease of the Second Affiliated Hospital of Soochow University","award":["ND2022B01"],"award-info":[{"award-number":["ND2022B01"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>Aim: The aim of this study is to investigate the mechanism and interaction of microRNA-181a (miR-181a), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-\u03baB) in gastric hypersensitivity in diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 65\u00a0mg\/kg) in female SD rats. Gastric balloon distension technique was used to measure diabetic gastric hypersensitivity. Gastric-specific (T7-T10) dorsal root ganglion (DRG) neurons were acutely dissociated to measure excitability with patch-clamp techniques. Western blotting was employed to measure the expressions of TLR4, TRAF6 and NF-\u03baB subunit p65 in T7-T10 DRGs. The expressions of microRNAs in T7-T10 DRGs were measured with quantitative real-time PCR and fluorescence in situ hybridization. Dual-luciferase reporter gene assay was used to detect the targeting regulation of microRNAs on TLR4. Results: (1) Diabetic rats were more sensitive to graded gastric balloon distention at 2 and 4\u00a0weeks. (2) The expression of TLR4 was significantly up-regulated in T7-T10 DRGs of diabetic rats. Intrathecal injection of CLI-095 (TLR4-selective inhibitor) attenuated diabetic gastric hypersensitivity, and markedly reversed the hyper-excitability of gastric-specific DRG neurons. (3) The expressions of miR-181a and miR-7a were significantly decreased in diabetic rats. MiR-181a could directly regulate the expression of TLR4, while miR-7a couldn\u2019t. (4) Intrathecal injection of miR-181a agomir down-regulated the expression of TLR4, reduced the hyper-excitability of gastric-specific neurons, and alleviated gastric hypersensitivity. (5) p65 and TLR4 were co-expressed in Dil-labeled DRG neurons. (6) Inhibition of p65 attenuated diabetic gastric hypersensitivity and hyper-excitability of gastric-specific DRG neurons. (7) The expression of TRAF6 was significantly up-regulated in diabetic rats. CLI-095 treatment also reduced the expression of TRAF6 and p65. Conclusion: The reduction of microRNA-181a in T7-T10 DRGs might up-regulate TLR4 expression. TLR4 activated NF-\u03baB through MyD88-dependent signaling pathway, increased excitability of gastric-specific DRG neurons, and contributed to diabetic gastric hypersensitivity.<\/jats:p>","DOI":"10.1177\/17448069231159356","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T22:48:07Z","timestamp":1675810087000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["microRNA-181a contributes to gastric hypersensitivity in rats with diabetes by regulating TLR4 expression"],"prefix":"10.1177","volume":"19","author":[{"given":"Qian","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing-Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency, The Affiliated Hospital of Jiangnan University, Wuxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Haian Hospital of Nantong University, Nantong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4232-8285","authenticated-orcid":false,"given":"Hong-Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou, China"},{"name":"Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"bibr1-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4711-2"},{"key":"bibr2-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0234-1"},{"key":"bibr3-17448069231159356","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000410"},{"key":"bibr4-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1068-13.2013"},{"key":"bibr5-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.03.002"},{"key":"bibr6-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001306"},{"key":"bibr7-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918807050"},{"key":"bibr8-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.06.001"},{"key":"bibr9-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3458-17.2018"},{"key":"bibr10-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001057"},{"key":"bibr11-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-019-01278-z"},{"key":"bibr12-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00577-0"},{"key":"bibr13-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-60"},{"key":"bibr14-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2010.01649.x"},{"key":"bibr15-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919838659"},{"key":"bibr16-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.134221"},{"key":"bibr17-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1038\/35053509"},{"key":"bibr18-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-01-00093.2002"},{"key":"bibr19-17448069231159356","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0138"},{"key":"bibr20-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1079"},{"key":"bibr21-17448069231159356","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"bibr22-17448069231159356","doi-asserted-by":"publisher","DOI":"10.5056\/jnm15091"},{"key":"bibr23-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13303"},{"key":"bibr24-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12035"},{"key":"bibr25-17448069231159356","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i28.8615"},{"key":"bibr26-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.18"},{"key":"bibr27-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01081.x"},{"key":"bibr28-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.11.057"},{"key":"bibr29-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2018.07.089"},{"key":"bibr30-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-0013-5"},{"key":"bibr31-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.116"},{"key":"bibr32-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155367"},{"key":"bibr33-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.12.022"},{"key":"bibr34-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1209775"},{"key":"bibr35-17448069231159356","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0376-2491.2018.34.014"},{"key":"bibr36-17448069231159356","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26316"},{"key":"bibr37-17448069231159356","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00142"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069231159356","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17448069231159356","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069231159356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:19:30Z","timestamp":1777709970000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17448069231159356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":37,"alternative-id":["10.1177\/17448069231159356"],"URL":"https:\/\/doi.org\/10.1177\/17448069231159356","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]},"article-number":"17448069231159356"}}