{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:36:52Z","timestamp":1789007812310,"version":"build-2803163510"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5-R01-DK117934"],"award-info":[{"award-number":["5-R01-DK117934"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5-R01-DK106286"],"award-info":[{"award-number":["5-R01-DK106286"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,4]]},"abstract":"<jats:p>\n                    Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and\/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 (\n                    <jats:italic>DEFA1A3<\/jats:italic>\n                    ) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the\n                    <jats:italic>DEFA1A3<\/jats:italic>\n                    locus are associated with UTI and pyelonephritis risk. Because\n                    <jats:italic>DEFA1A3<\/jats:italic>\n                    is not expressed in mice, we utilized human\n                    <jats:italic>DEFA1A3<\/jats:italic>\n                    gene transgenic mice (\n                    <jats:italic>\n                      DEFA\n                      <jats:sup>4\/4<\/jats:sup>\n                    <\/jats:italic>\n                    ) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (UPEC) stimulus in\u00a0vitro and in\u00a0vivo. We also demonstrate transgenic human\n                    <jats:italic>\n                      DEFA\n                      <jats:sup>4\/4<\/jats:sup>\n                    <\/jats:italic>\n                    gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the\n                    <jats:italic>DEFA1A3<\/jats:italic>\n                    locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2206515119","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T15:21:09Z","timestamp":1664205669000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic\n                    <i>Escherichia coli<\/i>\n                    challenge"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5323-7018","authenticated-orcid":false,"given":"Jorge J.","family":"Canas","sequence":"first","affiliation":[{"name":"Wells Center for Pediatric Research, Department of 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46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Kish","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH  44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Linn","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center at Nationwide Children\u2019s, The Ohio State University College of Veterinary Medicine, Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Bdeir","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania-Perelman School of Medicine, Philadelphia, PA 19104"},{"name":"Department of Medicine, University of Pennsylvania-Perelman School of Medicine, Philadelphia, PA 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