Article

Inflammation-activated CXCL16 pathway contributes to tubulointerstitial injury in mouse diabetic nephropathy

Authors: Ze-bo HU1, Kun-ling MA1, Yang ZHANG1, Gui-hua WANG1, Liang LIU1, Jian LU1, Pei-pei CHEN1, Chen-chen LU1, Bi-cheng LIU1
1 Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
Corresponding to: Kun-ling MA: klma05@163.com,
DOI: 10.1038/aps.2017.177
Received: 8 September 2017
Accepted: 19 November 2017
Advance online: 5 April 2018

Abstract

Abstract
Inflammation and lipid disorders play crucial roles in synergistically accelerating the progression of diabetic nephropathy (DN). In this study we investigated how inflammation and lipid disorders caused tubulointerstitial injury in DN in vivo and in vitro. Diabetic db/db mice were injected with 10% casein (0.5 mL, sc) every other day for 8 weeks to cause chronic inflammation. Compared with db/db mice, casein-injected db/db mice showed exacerbated tubulointerstitial injury, evidenced by increased secretion of extracellular matrix (ECM) and cholesterol accumulation in tubulointerstitium, which was accompanied by activation of the CXC chemokine ligand 16 (CXCL16) pathway. In the in vitro study, we treated HK-2 cells with IL-1β (5 ng/mL) and high glucose (30 mmol/L). IL-1β treatment increased cholesterol accumulation in HK-2 cells, leading to greatly increased ROS production, ECM protein expression levels, which was accompanied by the upregulated expression levels of proteins in the CXCL16 pathway. In contrast, after CXCL16 in HK-2 cells was knocked down by siRNA, the IL-1β-deteriorated changes were attenuated. In conclusion, inflammation accelerates renal tubulointerstitial lesions in mouse DN via increasing the activity of CXCL16 pathway.
Keywords: diabetic nephropathy; inflammation; IL-1β; CXCL16; cholesterol; tubular epithelium; db/db mice; HK-2 cells

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