Group 2 Innate Lymphoid Cells Participate in Renal Fibrosis in Diabetic Kidney Disease Partly via TGF- β 1 Signal Pathway

• Published in: Journal of diabetes research Vol. 2019; pp. 1 - 12
• Main Authors: Liu, Cuiping, Qin, Ludan, Ding, Jingya, Zhou, Luping, Gao, Chenlin, Zhang, Ting, Guo, Man, Huang, Wei, Jiang, Zongzhe, Long, Yang, Xu, Yong
• Format: Journal Article
• Language: English
• Published: England 03.07.2019
• Subjects: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Line; Collagen - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetic Nephropathies - blood; Female; Fibrosis; Humans; Immunity, Innate - drug effects; Interleukin-13 - blood; Interleukin-13 Receptor alpha1 Subunit - blood; Interleukin-4 - blood; Interleukin-4 Receptor alpha Subunit - blood; Interleukin-5 - blood; Kidney - pathology; Kidney Tubules, Proximal - metabolism; Lymphocytes - metabolism; Male; Middle Aged; Signal Transduction; Th2 Cells - cytology; Transforming Growth Factor beta1 - metabolism
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2019/8512028

Aim . To explore the role of group 2 innate lymphoid cells (ILC2s) in the pathogenesis of renal fibrosis in diabetic kidney disease (DKD). Methods . The proportion of ILC2s and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in the peripheral blood of normal control subjects (NC) or patients with type 2 diabetes mellitus (DM), early diabetic kidney disease (DKD1), or late diabetic kidney disease (DKD2) were analyzed by flow cytometry and ELISA. The expression of transforming growth factor- β 1 (TGF- β 1), fibronectin (FN), collagen1, IL-4R α , and IL-13R α 1 in renal tubular epithelial cells (HK-2) induced by IL-4, IL-13, or high glucose was analyzed by ELISA or qPCR. Results . The proportion of ILC2s and the levels of IL-4, IL-5, and IL-13 were significantly increased in DKD patients and were positively correlated with the severity of DKD ( P < 0.05 ). The expression of TGF- β 1, FN, and collagen1 was significantly upregulated in HK-2 cells induced by IL-4 or IL-13 ( P < 0.05 ). Moreover, the IL-4R α and IL-13R α 1 mRNA in HK2 cells were increased followed by high glucose alone or combined with IL-4 or IL-13, but the differences were not statistically significant ( P > 0.05 ). However, compared with high-glucose stimulation alone, the expression of TGF- β 1, FN, and collagen1 was significantly increased in HK-2 cells induced by high glucose combined with IL-4 or IL-13 ( P < 0.05 ). Conclusions . ILC2s may participate in renal fibrosis in DKD partly via TGF- β 1 signal pathway.