Journal
RHEUMATOLOGY
Volume 61, Issue 9, Pages 3830-3840Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keac037
Keywords
mTOR; lupus nephritis; proteomics; bioinformatics; rapamycin
Categories
Funding
- National Natural Science Foundation of China [81870479]
- Beijing Natural Science Foundation [7192207, 7212114]
- Chinese Academy of Medical Sciences Research Unit [2019RU023]
- Clinical Medicine Plus X-Young Scholars Project of Peking University
- Fundamental Research Funds for the Central Universities
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This study evaluated the activation of mammalian target of rapamycin (mTOR) in renal tissue of LN patients. The activation of mTORC1/2 was found to be significantly increased in different cell types of LN patients compared to controls, and mTORC1 activation was strongly associated with clinical and pathological indicators of LN. The study also identified mTORC1 activation as a prognostic marker in LN patients.
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.
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