{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:08:22Z","timestamp":1782421702344,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3K2421"],"award-info":[{"award-number":["CMRPG3K2421"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3L0791"],"award-info":[{"award-number":["CMRPG3L0791"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 110-2314-B-182A-017"],"award-info":[{"award-number":["MOST 110-2314-B-182A-017"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Approximately 1 million cases of leptospirosis, an emerging infectious zoonotic disease, are reported each year. Pathogenic Leptospira species express leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic Leptospira species. The LRR domain-containing protein family is vital for the virulence of pathogenic Leptospira species. In this study, the biological mechanisms of an essential LRR domain protein from pathogenic Leptospira were examined. The effects of Leptospira and recombinant LRR20 (rLRR20) on the expression levels of factors involved in signal transduction were examined using microarray, quantitative real-time polymerase chain reaction, and western blotting. The secreted biomarkers were measured using an enzyme-linked immunosorbent assay. rLRR20 colocalized with E-cadherin on the cell surface and activated the downstream transcription factor \u03b2-catenin, which subsequently promoted the expression of MMP7, a kidney injury biomarker. Additionally, MMP7 inhibitors were used to demonstrate that the secreted MMP7 degrades surface E-cadherin. This feedback inhibition mechanism downregulated surface E-cadherin expression and inhibited the colonization of Leptospira. The degradation of surface E-cadherin activated the NF-\u03baB signal transduction pathway. Leptospirosis-associated acute kidney injury is associated with the secretion of NGAL, a downstream upregulated biomarker of the NF-\u03baB signal transduction pathway. A working model was proposed to illustrate the crosstalk between E-cadherin\/\u03b2-catenin and NF-\u03baB signal transduction pathways during Leptospira infection. Thus, rLRR20 of Leptospira induces kidney injury in host cells and inhibits the adhesion and invasion of Leptospira through the upregulation of MMP7 and NGAL.<\/jats:p>","DOI":"10.3390\/ijms222313132","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"13132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Crosstalk between E-Cadherin\/\u03b2-Catenin and NF-\u03baB Signaling Pathways: The Regulation of Host-Pathogen Interaction during Leptospirosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-4151","authenticated-orcid":false,"given":"Shen-Hsing","family":"Hsu","sequence":"first","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Fang","family":"Chou","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hung","family":"Hong","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0376","authenticated-orcid":false,"given":"Ming-Yang","family":"Chang","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ying","family":"Tsai","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chung","family":"Tian","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-9717","authenticated-orcid":false,"given":"Huang-Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1080\/0886022X.2020.1721300","article-title":"A long journey for acute kidney injury biomarkers","volume":"42","author":"Oh","year":"2020","journal-title":"Ren. 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