PMID- 35040950 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20221102 IS - 1462-0332 (Electronic) IS - 1462-0324 (Print) IS - 1462-0324 (Linking) VI - 61 IP - 9 DP - 2022 Aug 30 TI - Renal mTORC1 activation is associated with disease activity and prognosis in lupus nephritis. PG - 3830-3840 LID - 10.1093/rheumatology/keac037 [doi] AB - OBJECTIVE: This study was initiated to evaluate mammalian target of rapamycin (mTOR) activation in renal tissue of LN patients. METHODS: This retrospective study included 187 LN patients, 20 diabetic nephropathy (DN) patients, 10 minimal change disease (MCD) patients and 10 normal controls (NCs). Seven of 187 LN patients had repeated renal biopsies. mTORC1/2 activation was evaluated by immunohistochemistry and multiplexed immunofluorescence. The association of mTORC1/2 activation with the clinicopathologic indices and prognostic outcomes was analysed among 187 LN patients. Proteomics was performed in renal biopsies of 20 LN patients. Proteomics was employed to comprehensively evaluate the impact of mTOR activation on intrarenal gene expression. RESULTS: mTORC1/2 was significantly activated in podocytes, mesangial cells, endothelial cells and tubular epithelial cells of LN patients as compared with those with MCD or NC. The glomerular mTORC1 activation was higher in LN patients compared with DN patients. mTORC1, but not mTORC2, activation strongly correlated with serum albumin, complement C3, proteinuria and the following pathological biomarkers of LN: crescent formation, interstitial inflammation and fibrosis. Moreover, mTORC1 activation was identified as a prognostic marker in LN patients. Bioinformatic analyses of proteomics and immunohistochemical data unveiled increased complement activation, antigen presentation and phagocytosis in LN patients with mTORC1 activation. CONCLUSION: Renal mTORC1 activation could be a biomarker to reveal disease activity and predict clinical prognosis in LN patients. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Mao, Zhaomin AU - Mao Z AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. AD - Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University. FAU - Tan, Ying AU - Tan Y AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. FAU - Tao, Juan AU - Tao J AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. FAU - Li, Linlin AU - Li L AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. FAU - Wang, Hui AU - Wang H AD - Laboratory of Electron Microscopy, Department of Medicine, Peking University First Hospital. FAU - Yu, Feng AU - Yu F AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. AD - Department of Nephrology, Peking University International Hospital, Beijing, PR China. FAU - Perl, Andras AU - Perl A AD - Departments of Medicine, Microbiology and Immunology, Biochemistry and Molecular Biology, State University of New York Upstate Medical University, New York, Syracuse, NY, USA. FAU - Zhao, Minghui AU - Zhao M AD - Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China. AD - Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University. LA - eng GR - R01 AI072648/AI/NIAID NIH HHS/United States GR - R01 AI122176/AI/NIAID NIH HHS/United States GR - R34 AI141304/AI/NIAID NIH HHS/United States GR - U01 AR076092/AR/NIAMS NIH HHS/United States PT - Journal Article PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Biomarkers) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) SB - IM MH - Biomarkers/metabolism MH - Endothelial Cells/metabolism MH - Humans MH - Kidney/pathology MH - *Lupus Nephritis MH - Mechanistic Target of Rapamycin Complex 1/metabolism MH - Prognosis MH - Retrospective Studies PMC - PMC9608003 OTO - NOTNLM OT - bioinformatics OT - lupus nephritis OT - mTOR OT - proteomics OT - rapamycin EDAT- 2022/01/19 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/01/18 CRDT- 2022/01/18 12:32 PHST- 2021/10/14 00:00 [received] PHST- 2022/01/11 00:00 [revised] PHST- 2022/01/19 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/01/18 12:32 [entrez] PHST- 2022/01/18 00:00 [pmc-release] AID - 6510926 [pii] AID - keac037 [pii] AID - 10.1093/rheumatology/keac037 [doi] PST - ppublish SO - Rheumatology (Oxford). 2022 Aug 30;61(9):3830-3840. doi: 10.1093/rheumatology/keac037.