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Next, we examined the role of APOL1 in the podocyte stress and the inflammatory signaling in the kidney after hemi-nephrectomy.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>We identified a novel RNA variant that lacks a secretory pathway signal sequence and we found that the predicted APOL1-B3 protein isoform was expressed in human podocytes in vivo and by BAC-APOL1 transgenic mice. APOL1-B3-G2 transgenic mice, carrying a renal risk variant, manifested podocyte injury and increased pro-IL-1\u03b2 mRNA in isolated glomeruli and increased IL-1\u03b2 production in the remnant kidney after uninephrectomy. APOL1-B3 interacted with NLRP12, a key regulator of Toll-like receptor signaling.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>These results suggest a possible mechanism for podocyte injury by which one of the APOL1 protein isoforms, APOL1-B3 and its renal risk variants, enhances inflammatory signaling.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12882-020-01995-3","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T13:04:15Z","timestamp":1598533455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["APOL1 renal risk variants exacerbate podocyte injury by increasing inflammatory stress"],"prefix":"10.1186","volume":"21","author":[{"given":"Hidefumi","family":"Wakashin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen","family":"Heymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hila","family":"Roshanravan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parnaz","family":"Daneshpajouhnejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Kyun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Hoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-186X","authenticated-orcid":false,"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"issue":"5993","key":"1995_CR1","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1193032","volume":"329","author":"G Genovese","year":"2010","unstructured":"Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. 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