{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T21:05:54Z","timestamp":1777928754088,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T00:00:00Z","timestamp":1549756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Kazato Research Grants, Japan"},{"name":"Grant-in-Aid for Scientific Research to a Graduate Student from the Graduate School of Veterinary Medicine, Hokkaido University, Japan","award":["Grant-in Aid FY 2017"],"award-info":[{"award-number":["Grant-in Aid FY 2017"]}]},{"name":"Grant-in-Aid for Scientific Research to a Graduate Student from the Graduate School of Veterinary Medicine, Hokkaido University, Japan","award":["PH36150001"],"award-info":[{"award-number":["PH36150001"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lupus"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and\/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood\u2013urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Lupus-prone BXSB\/MpJ-Yaa (Yaa) and BXSB\/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24\u2009wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24\u2009wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24\u2009wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24\u2009wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P\u2009&lt;\u20090.05 and 0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0961203319828518","type":"journal-article","created":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T23:29:01Z","timestamp":1549841341000},"page":"324-333","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice"],"prefix":"10.1177","volume":"28","author":[{"given":"M A","family":"Masum","sequence":"first","affiliation":[{"name":"Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan"},{"name":"Department of Anatomy, Histology and Physiology, Faculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-5510","authenticated-orcid":false,"given":"O","family":"Ichii","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y H A","family":"ELewa","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan"},{"name":"Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Kon","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,2,10]]},"reference":[{"key":"bibr1-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq062"},{"key":"bibr2-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2430-y"},{"key":"bibr3-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V7122495"},{"key":"bibr4-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005101085"},{"key":"bibr5-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-017-0694-3"},{"key":"bibr6-0961203319828518","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1681\/ASN.V11147","volume":"11","author":"Ohashi R","year":"2000","journal-title":"J Am Soc 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Overexpression of Toll-like receptor 9 correlates with podocyte injury in a murine model of autoimmune membranoproliferative glomerulonephritis.\n                      Autoimmunity\n                      (Submitted, under revision)."},{"key":"bibr26-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28617-1"},{"key":"bibr27-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.148"},{"key":"bibr28-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008010123"},{"key":"bibr29-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.67097.x"},{"key":"bibr30-0961203319828518","first-page":"317","volume":"21","author":"Pichler R","year":"1995","journal-title":"Miner Electrolyte Metab"},{"key":"bibr31-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.350"},{"key":"bibr32-0961203319828518","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803044"},{"key":"bibr33-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184330"},{"key":"bibr34-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1177\/1753425915606525"},{"key":"bibr35-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"bibr36-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00729.x"},{"key":"bibr37-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23025"},{"key":"bibr38-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2006.07.023"},{"key":"bibr39-0961203319828518","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-05-0323"}],"container-title":["Lupus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0961203319828518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0961203319828518","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0961203319828518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:20:36Z","timestamp":1777677636000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0961203319828518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,10]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1177\/0961203319828518"],"URL":"https:\/\/doi.org\/10.1177\/0961203319828518","relation":{},"ISSN":["0961-2033","1477-0962"],"issn-type":[{"value":"0961-2033","type":"print"},{"value":"1477-0962","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,10]]}}}