{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:38:54Z","timestamp":1787611134548,"version":"build-2736575974"},"reference-count":27,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney Dis"],"abstract":"<jats:p>Introduction: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is characterized by persistent immune dysregulation and glomerular injury predominantly driven by macrophage infiltration and type I interferon (IFN-I) signaling. Crosstalk between injured podocytes and infiltrating macrophages is increasingly recognized as a key contributor to LN progression; however, the molecular mediators and their corresponding receptors remain poorly defined. This study investigates whether ANGPTL3 upregulation in podocytes activates macrophages through MSR1 and drives interferon-biased inflammation in LN. Methods: We employed secretome-based protein-protein interaction screening to identify ANGPTL3 receptors. The ANGPTL3-MSR1 interaction was supported by co-immunoprecipitation. In vitro, bone marrow-derived macrophages (BMDMs) were stimulated with ANGPTL3-conditioned media, and gene expression was analyzed by RNA sequencing. MSR1 was silenced using siRNA. In vivo, a pristane-induced lupus mouse model was used to assess glomerular ANGPTL3\/MSR1 expression, renal function, and macrophage infiltration. Clinical relevance was assessed using Nephroseq datasets and human LN kidney specimens. Results: ANGPTL3 was identified as an MSR1-interacting ligand through a cell-based membrane protein screening assay and further supported by co-immunoprecipitation. In vitro, ANGPTL3-conditioned media induced an interferon-dominant transcriptional response in BMDMs, including upregulation of Tnip3 and Isg20. These effects were attenuated upon MSR1 silencing, confirming receptor-dependent activation. Notably, ANGPTL3 had minimal effect on M1\/M2 polarization markers, indicating selective regulation of interferon signaling. Analysis of Nephroseq datasets and LN biopsies demonstrated elevated ANGPTL3 and MSR1 expression, which correlated with histopathological severity. Single-cell RNA-seq confirmed MSR1 enrichment in glomerular macrophages. In vivo, pristane-induced lupus mice exhibited increased glomerular ANGPTL3, Synaptopodin loss, proteinuria, and colocalization of F4\/80 and MSR1, supporting a pathogenic podocyte-macrophage axis. Conclusion: This study identifies the ANGPTL3-MSR1 axis as a critical pathway linking podocyte injury to macrophage-driven inflammation in LN, highlighting its therapeutic potential. Targeting this axis may disrupt maladaptive immune crosstalk, offering a novel strategy for LN management.<\/jats:p>","DOI":"10.1159\/000550803","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:01:54Z","timestamp":1770138114000},"page":"288-301","source":"Crossref","is-referenced-by-count":1,"title":["ANGPTL3 in Podocytes Contributes to the Pathogenesis of Lupus Nephritis by Activating MSR1 in Macrophages"],"prefix":"10.1159","volume":"12","author":[{"given":"Qianying","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0141-9"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203316646861"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601565"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100998"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00722-z"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.10.014"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00826-z"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-024-00811-4"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.148109"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02698-x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2023.01.008"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-019-1383-1"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05313-7"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1228399"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109715"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4312"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01285-6"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.012"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.457"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0398-x"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317128"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2022.23.12.4315"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2025.0038"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1012002"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2023.04.004"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40635-w"}],"container-title":["Kidney Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000550803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:01:26Z","timestamp":1774371686000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000550803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000550803","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.31239385","asserted-by":"subject"}]},"ISSN":["2296-9381","2296-9357"],"issn-type":[{"value":"2296-9381","type":"print"},{"value":"2296-9357","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]}}}