{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:40:45Z","timestamp":1792798845045,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Unit","award":["2019RU023"],"award-info":[{"award-number":["2019RU023"]}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Natural Science Foundation","award":["7212114"],"award-info":[{"award-number":["7212114"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.82000666"],"award-info":[{"award-number":["No.82000666"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peking University International Hospital Research Grant","award":["No. YN2020ZD03"],"award-info":[{"award-number":["No. YN2020ZD03"]}],"id":[{"id":"https:\/\/ror.org\/03jxhcr96","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Peking University Clinical Scientist Training Program supported by \u201cthe Fundamental Research Funds for the Central Universities\u201d","id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2023,4,15]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was initiated to evaluate the mammalian target of the rapamycin (mTOR) signalling pathway involved in renal endothelial-podocyte crosstalk in patients with lupus nephritis (LN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared the kidney protein expression patterns of 10 patients with LN with severe endothelial-podocyte injury and 3 patients with non-severe endothelial-podocyte injury on formalin-fixed paraffin-embedded kidney tissues using label-free liquid chromatography-mass spectrometry for quantitative proteomics analysis. Podocyte injury was graded by foot process width (FPW). The severe group was referred to patients with both glomerular endocapillary hypercellularity and FPW &gt;1240 nm. The non-severe group included patients with normal endothelial capillaries and FPW in the range of 619~1240 nm. Gene Ontology (GO) enrichment analyses were performed based on the protein intensity levels of differentially expressed proteins in each patient. An enriched mTOR pathway was selected, and the activation of mTOR complexes in renal biopsied specimens was further verified in 176 patients with LN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with those of the non-severe group, 230 proteins were upregulated and 54 proteins were downregulated in the severe group. Furthermore, GO enrichment analysis showed enrichment in the \u2018positive regulation of mTOR signalling\u2019 pathway. The glomerular activation of mTOR complex 1 (mTORC1) was significantly increased in the severe group compared with the non-severe group (p=0.034), and mTORC1 was located in podocytes and glomerular endothelial cells. Glomerular activation of mTORC1 was positively correlated with endocapillary hypercellularity (r=0.289, p&lt;0.001) and significantly increased in patients with both endocapillary hypercellularity and FPW &gt;1240 nm (p&lt;0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Glomerular mTORC1 was highly activated in patients with both glomerular endocapillary hypercellularity and podocyte injury, which might be involved in podocytes to endothelial cells communication in lupus nephritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2023-000896","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T10:11:31Z","timestamp":1683281491000},"page":"e000896","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Glomerular mTORC1 activation was associated with podocytes to endothelial cells communication in lupus nephritis"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-0782","authenticated-orcid":false,"given":"Xiaotian","family":"Liu","sequence":"first","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-7252","authenticated-orcid":false,"given":"Zhaomin","family":"Mao","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-0106","authenticated-orcid":false,"given":"Mo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Li","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, Beijing, China"},{"name":"Institute of Nephrology, Peking University, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-6233","authenticated-orcid":false,"given":"Feng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Peking University International Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"2025091514161044000_10.1.e000896.1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41572-019-0141-9","article-title":"Lupus nephritis","volume":"6","author":"Anders","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2025091514161044000_10.1.e000896.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.85"},{"key":"2025091514161044000_10.1.e000896.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.11.023"},{"key":"2025091514161044000_10.1.e000896.4","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.409"},{"key":"2025091514161044000_10.1.e000896.5","doi-asserted-by":"crossref","DOI":"10.1186\/ar4142","article-title":"The spectrum of renal thrombotic microangiopathy in lupus nephritis","volume":"15","author":"Song","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"2025091514161044000_10.1.e000896.6","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket491"},{"key":"2025091514161044000_10.1.e000896.7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1177\/0961203319828509","article-title":"The associations of endothelial and podocyte injury in proliferative lupus nephritis: from observational analysis to in vitro study","volume":"28","author":"Yuan","year":"2019","journal-title":"Lupus"},{"key":"2025091514161044000_10.1.e000896.8","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.kint.2019.05.007","article-title":"Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells","volume":"96","author":"Ebefors","year":"2019","journal-title":"Kidney Int"},{"key":"2025091514161044000_10.1.e000896.9","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1016\/j.ekir.2021.04.013","article-title":"Endothelial endothelin receptor A expression is associated with podocyte injury and oxidative stress in patients with focal segmental glomerulosclerosis","volume":"6","author":"van de Lest","year":"2021","journal-title":"Kidney Int Rep"},{"key":"2025091514161044000_10.1.e000896.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71195"},{"key":"2025091514161044000_10.1.e000896.11","doi-asserted-by":"crossref","unstructured":"van Aanhold CCL , Bos M , Mirabito Colafella KM , et al . n.d. Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia. Sci Rep;11. doi:10.1038\/s41598-021-85040-9","DOI":"10.1038\/s41598-021-85040-9"},{"key":"2025091514161044000_10.1.e000896.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3522"},{"key":"2025091514161044000_10.1.e000896.13","doi-asserted-by":"publisher","DOI":"10.1038\/nri3901"},{"key":"2025091514161044000_10.1.e000896.14","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008111186"},{"key":"2025091514161044000_10.1.e000896.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.108"},{"key":"2025091514161044000_10.1.e000896.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.05.008"},{"key":"2025091514161044000_10.1.e000896.17","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1093\/rheumatology\/keac037","article-title":"Renal mTORC1 activation is associated with disease activity and prognosis in lupus nephritis","volume":"61","author":"Mao","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"2025091514161044000_10.1.e000896.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.02.003"},{"key":"2025091514161044000_10.1.e000896.19","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/anr.1780320909","article-title":"Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus","volume":"32","author":"Liang","year":"1989","journal-title":"Arthritis Care Res"},{"key":"2025091514161044000_10.1.e000896.20","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"2025091514161044000_10.1.e000896.21","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1177\/09612033221094711","article-title":"Proteomic profiling of kidney samples in patients with pure membranous and proliferative lupus nephritis","volume":"31","author":"Chen","year":"2022","journal-title":"Lupus"},{"key":"2025091514161044000_10.1.e000896.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312890"},{"key":"2025091514161044000_10.1.e000896.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax3939"},{"key":"2025091514161044000_10.1.e000896.24","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.75"},{"key":"2025091514161044000_10.1.e000896.25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bbrc.2020.02.088","article-title":"Protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes","volume":"525","author":"Yoshibayashi","year":"2020","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2025091514161044000_10.1.e000896.26","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1039\/C6MB00195E","article-title":"Autophagy is involved in regulating VEGF during high-glucose-induced podocyte injury","volume":"12","author":"Miaomiao","year":"2016","journal-title":"Mol Biosyst"},{"key":"2025091514161044000_10.1.e000896.27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000132"},{"key":"2025091514161044000_10.1.e000896.28","doi-asserted-by":"publisher","DOI":"10.1191\/0961203302lu131oa"},{"key":"2025091514161044000_10.1.e000896.29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bbrc.2021.11.030","article-title":"Substrate stiffening promotes VEGF-A functions via the PI3K\/Akt\/mTOR pathway","volume":"586","author":"Husain","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"2025091514161044000_10.1.e000896.30","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005080810"},{"key":"2025091514161044000_10.1.e000896.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707330"},{"key":"2025091514161044000_10.1.e000896.32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44771"},{"key":"2025091514161044000_10.1.e000896.33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44774"},{"key":"2025091514161044000_10.1.e000896.34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trsl.2022.03.004","article-title":"Cell type-specific mechanistic target of rapamycin-dependent distortion of autophagy pathways in lupus nephritis","volume":"245","author":"Caza","year":"2022","journal-title":"Translational Research"},{"key":"2025091514161044000_10.1.e000896.35","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.4049\/jimmunol.165.9.5338","article-title":"Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c","volume":"165","author":"Sieling","year":"2000","journal-title":"The Journal of Immunology"},{"key":"2025091514161044000_10.1.e000896.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30485-9"},{"key":"2025091514161044000_10.1.e000896.37","doi-asserted-by":"crossref","first-page":"108781","DOI":"10.1016\/j.clim.2021.108781","article-title":"Improvement of renal and non-renal SLE outcome measures on sirolimus therapy-a 21-year follow-up study of 73 patients","volume":"229","author":"Piranavan","year":"2021","journal-title":"Clin Immunol"},{"key":"2025091514161044000_10.1.e000896.38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2012.01646.x"},{"key":"2025091514161044000_10.1.e000896.39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8338"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2023-000896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T21:16:19Z","timestamp":1757970979000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2023-000896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,5,5]]},"published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1136\/lupus-2023-000896"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2023-000896","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1878924\/v1","asserted-by":"object"}]},"ISSN":["2053-8790"],"issn-type":[{"value":"2053-8790","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5]]}}}