{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:26:55Z","timestamp":1788964015045,"version":"build-2803163510"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"General Program of National Natural Science Foundation of China","award":["82372181"],"award-info":[{"award-number":["82372181"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sepsis-associated acute kidney injury (SAKI) is a leading cause of critical illness and death, yet its upstream drivers remain unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies innate immune signaling. We investigated whether TREM-1 acts upstream of the NLRP3 inflammasome to promote pyroptotic injury in septic kidneys, while documenting accompanying changes in autophagy. Male mice with genetic deletion of\n                    <jats:italic>Trem1<\/jats:italic>\n                    and wild-type littermates underwent cecal ligation and puncture; kidneys and serum were collected at 24\u00a0h. A subset received pharmacologic modulation of the NLRP3 inflammasome (MCC950 inhibitor or nigericin activator). Renal injury was assessed by histology and tubular injury scores, serum creatinine and blood urea nitrogen, and cytokines. Inflammasome and pyroptosis readouts (NLRP3, cleaved caspase-1, cleaved gasdermin D, interleukin-1\u03b2) and autophagy markers (LC3B, Beclin-1, Atg5) were measured by Western blot and enzyme-linked immunosorbent assay. In human proximal tubular epithelial cells (HK-2), TREM-1 was overexpressed or silenced and cells were stimulated with lipopolysaccharide; the same readouts were quantified.\n                    <jats:italic>Trem1<\/jats:italic>\n                    deletion reduced kidney injury after sepsis, with lower tubular injury scores, improved serum creatinine and blood urea nitrogen, and decreased circulating cytokines. Renal inflammasome\u2013pyroptosis activity was blunted in\n                    <jats:italic>Trem1<\/jats:italic>\n                    -deficient mice, with reduced NLRP3, cleaved caspase-1, cleaved gasdermin D, and interleukin-1\u03b2. Pharmacologic modulation aligned with this axis: MCC950 lessened injury in wild-type mice, whereas nigericin aggravated injury despite\n                    <jats:italic>Trem1<\/jats:italic>\n                    deficiency. In tubular cells, TREM-1 overexpression increased NLRP3 activation, interleukin-1\u03b2 release, and pyroptosis markers, while TREM-1 knockdown produced the opposite pattern. Across models,\n                    <jats:italic>Trem1<\/jats:italic>\n                    loss or inhibition was associated with higher autophagy markers. Limited to the autophagy non-perturbed experimentally, these increases are interpreted as concomitant rather than causal. TREM-1 functions as an upstream amplifier of NLRP3 inflammasome activation and pyroptotic tubular injury in SAKI. Autophagy marker changes accompanied TREM1 loss; their functional relevance to NLRP3 activation remains to be determined. These data support soluble TREM-1 as a candidate early biomarker and nominate TREM-1 as a therapeutic target. Future work should define time courses, test post-insult TREM-1 blockade, and link circulating or urinary TREM-1 with renal inflammasome signatures to refine risk stratification and guide intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-40893-w","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:44:14Z","timestamp":1773942254000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TREM1\u2013NLRP3\u2013driven pyroptosis in sepsis-associated acute kidney injury (AKI) with parallel autophagy changes"],"prefix":"10.1038","volume":"16","author":[{"given":"Xudong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxiang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"40893_CR1","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1097\/MCC.0000000000000150","volume":"20","author":"W. 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