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

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.

• Authors: Ze-Bo Hu, Kun-Ling Ma, Yang Zhang, Gui-Hua Wang, Liang Liu, Jian Lu, Pei-Pei Chen, Chen-Chen Lu, Bi-Cheng Liu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 39 Issue 6 Pg. 1022-1033 (Jun 2018) ISSN: 1745-7254 [Electronic] United States
• PMID: 29620052 (Publication Type: Journal Article)

Chemical References

• CXCL16 protein, human
• Caseins
• Chemokine CXCL16
• Cxcl16 protein, mouse
• Extracellular Matrix Proteins
• Inflammation Mediators
• Reactive Oxygen Species
• Cholesterol

Topics

• Animals
• Caseins
• Cell Line
• Chemokine CXCL16 (genetics, metabolism)
• Cholesterol (metabolism)
• Diabetic Nephropathies (genetics, metabolism, pathology)
• Disease Models, Animal
• Extracellular Matrix Proteins (metabolism)
• Humans
• Inflammation (chemically induced, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Kidney Tubules (metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Time Factors