{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:36:03Z","timestamp":1791286563117,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tubulointerstitial inflammation and fibrosis are strongly associated with the outcome of chronic kidney disease. We recently demonstrated that the NOD-like receptor, pyrin domain containing-3 (NLRP3) contributes to renal inflammation, injury, and fibrosis following unilateral ureteric obstruction in mice. NLRP3 expression in renal tubular epithelial cells (TECs) was found to be an important component of experimental disease pathogenesis, although the biology of NLRP3 in epithelial cells is unknown. In human and mouse primary renal TECs, NLRP3 expression was increased in response to TGF-\u03b21 stimulation and associated with epithelial\u2013mesenchymal transition (EMT) and the expression of \u03b1-smooth muscle actin (\u03b1SMA) and matrix metalloproteinase (MMP) 9. TGF-\u03b21\u2013induced EMT and the induction of MMP-9 and \u03b1SMA were significantly decreased in mouse Nlrp3\u2212\/\u2212 renal TECs, suggesting a role for Nlrp3 in TGF-\u03b2\u2013dependent signaling. Although apoptosis-associated speck-like protein containing a CARD domain\u2212\/\u2212 TECs demonstrated a phenotype similar to that of Nlrp3\u2212\/\u2212 cells in response to TGF-\u03b21, the effect of Nlrp3 on MMP-9 and \u03b1SMA expression was inflammasome independent, as IL-1\u03b2, IL-18, MyD88, and caspase-1 were dispensable. Smad2 and Smad3 phosphorylation in response to TGF-\u03b21 was attenuated in Nlrp3\u2212\/\u2212 and apoptosis-associated speck-like protein containing a CARD domain\u2212\/\u2212 cells, accounting for the dampened EMT and TGF-\u03b21 responsiveness in these cells. Consistent with these findings, overexpression of NLRP3 in 293T cells resulted in increased Smad3 phosphorylation and activity. Taken together, these data support a novel and direct role for NLRP3 in promoting TGF-\u03b2 signaling and R-Smad activation in epithelial cells independent of the inflammasome.<\/jats:p>","DOI":"10.4049\/jimmunol.1201959","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T07:13:02Z","timestamp":1356160382000},"page":"1239-1249","source":"Crossref","is-referenced-by-count":233,"title":["Inflammasome-Independent NLRP3 Augments TGF-\u03b2 Signaling in Kidney Epithelium"],"prefix":"10.1093","volume":"190","author":[{"given":"Wenjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akosua","family":"Vilaysane","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"French","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A","family":"Bracey","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiril","family":"Trpkov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Bonni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]},{"name":"Southern Alberta Cancer Research Institute, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J","family":"Duff","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A","family":"Muruve","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta T2N 1N4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,1]]},"reference":[{"issue":"4","key":"2025032406281058100_r1","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1053\/ajkd.2001.27392","article-title":"Cardiovascular disease in end-stage renal disease patients","volume":"38","author":"Collins","year":"2001","journal-title":"Am. 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