Increased expression of toll-like receptor 2 in rat diabetic nephropathy.
OBJECTIVE
Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). This study examined the role of Toll-like receptor 2 (TLR2) in the progression of renal injury in a model of rat DN.


METHODS
DN was induced by intravenous injection of streptozotocin and rats were sacrificed at week 2, 4 and 8. Functional and pathologic markers, inflammatory infiltration, expression of TLR2, MCP-1, MyD88, HSP70, HMGB1 and activation of NF-kappaB were assessed. The effects of glucose on the expression of TLR2 by renal tubular epithelial cells were also examined in vitro.


RESULTS
The expression of TLR2 mRNA and protein level was significantly upregulated in the kidneys of diabetic rats (p < 0.01), which was associated with increased renal expression of MyD88 and MCP-1, activation of NF-kappaB and infiltration of macrophages. The expression of HSP70 and HMGB1, endogenous ligands of TLRs, was also significantly upregulated in the kidneys of diabetic rats. In human renal biopsy of DN, there was prominent expression of TLR2 in both the glomeruli and tubulointerstitium. In vitro study showed that high glucose induced the expression of TLR2 mRNA by NRK-52E cells (p < 0.01).


CONCLUSIONS
Enhanced renal expression of TLR2 is associated with inflammatory infiltration in DN.
Li
Fanglin
F
Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yang
Niansheng
N
Zhang
Lili
L
Tan
Hechang
H
Huang
Bin
B
Liang
Yingjie
Y
Chen
Miaoyan
M
Yu
Xueqing
X
D000328:Adult; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D024243:HMGB1 Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; C104200:Hbp1 protein, rat; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495342:TLR2 protein, human; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D013311:Streptozocin