Interleukin-7 Is Associated with Clinical and Pathological Activities in Immunoglobulin A Nephropathy and Protects the Renal Proximal Tubule Epithelium from Cellular Fibrosis

Objective:Diagnosis of immunoglobulin A nephropathy(IgAN)requires the evaluation of renal biopsy specimens.However,renal biopsy is an invasive procedure and is not frequently performed for various reasons.Thus,recognized noninvasive biomarkers for predicting IgAN progression are urgently needed.Methods:In the present study,we included 86 IgAN patients with renal biopsy from June 2015 to May 2016 and had their plasma interleukin-7(IL-7)level measured with ELISA.The association between the plasma IL-7 level and clinico-pathological characteristics was analyzed.Immunohistochemical staining was used to assay the in situ expression of IL-7 in vivo.Western blotting was perfonned to examine the production of extracellular matrix,p-mTOR and the markers of autophagy under the treatment of IL-7 after TGF-β1 stimulation in renal tubular epithelial cells.Results:IL-7 was significantly decreased in patients with IgAN compared to healthy subjects(2.3077 vs.8.6294 pg/mL,P<0.0001).There was a significant difference in the plasma IL-7 level between tubular atrophy/interstitial fibrosis TO and T2 classes(P=0.0064).A lower plasma IL-7 value in patients at the time of biopsy indicated a poor renal outcome.In addition,IL-7 was over-expressed in renal tubular epithelial cells and significantly attenuated transforming growth factor β1-induced extracellular matrix production by suppression of cellular autophagy via activation of mTOR1 signaling.Conclusion:These results suggested that IL-7 might be a noninvasive biomarker for predicating IgAN.It protected renal proximal tubular epithelial cells from cellular fibrosis by inhibiting autophagy via mTORl signaling.