Crosstalk between monocytes and renal mesangial cells via interaction of metalloproteinases and fractalkine in diabetic nephropathy.
An increasing number of studies suggest that the activation of innate immunity with the development of a chronic low‑grade inflammatory response is a factor in the pathogenesis of diabetic nephropathy (DN). Advanced glycation end products (AGEs), chemokines and matrix metalloproteinases (MMPs) are known to be important in inflammatory reactions in DN. In the present study, the inter-regulation of MMP2 and fractalkine was observed between monocytes (U937) and human renal mesangial cells (HRMCs) and its potential pathophysiological role in DN. The expression of fractalkine and MMP2 was analyzed by RT-PCR, western blot analysis and enzyme‑linked immunosorbent assay. The chemotaxis and adhesiveness of HRMCs to U937 cells was detected with a transwell system, co‑culture and fluorescent staining, respectively. The results showed a decreased expression of MMP2 and an increased expression of fractalkine by AGEs in HRMCs. Fractalkine downregulated the mRNA expression and activity of MMP2, and the reduced MMP2 activity was reversed with an anti‑fractalkine antibody. Conversely, MMP2 upregulated fractalkine mRNA and protein expression in HRMCs, which led to an increase in chemotaxis and a decrease in monocytic adhesion to HRMCs. In conclusion, these observations suggest a crosstalk between monocytes and HRMCs via the interaction of MMP2 and fractalkine, which may represent a therapeutic target to impede the inflammatory process associated with DN.
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Yanping
Y
Wang
Qiong
Q
Wei
Qiang
Q
Liu
Zheng
Z
Li
Li
L
Zhou
Fang
F
Zou
Yang
Y
Yuan
Zilin
Z
Sun
D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D054428:Chemokine CX3CL1; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2