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Increased Renal Expression of Adhesion Molecules and Inflammation in Diabetic Nephropathy
Author(s) -
FAN LETAO,
He Xiaochen,
Muroya Yoshikazu,
Fan Fan,
Roman Richard J.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.573.7
Subject(s) - medicine , diabetic nephropathy , endocrinology , glomerular basement membrane , nephropathy , inflammation , glomerulosclerosis , fibrosis , cell adhesion molecule , creatinine , renal function , cytokine , kidney disease , kidney , proteinuria , diabetes mellitus , immunology
Diabetic nephropathy (DN) is the primary risk factor for end‐stage renal disease (ESRD). Previously, we reported that the T2DN rat develops hyperglycemia by 3 months of age, proteinuria by 6 months and progressive renal injury which closely mimics human diabetic nephropathy, including focal glomerular sclerosis, mesangial matrix expansion, thickening of basement membranes, and progressive renal interstitial fibrosis. However, the role of adhesion molecules and renal inflammation in the pathogenesis of DN in this model has not been studied. In the present study, we compared the expression of cytokine and adhesion molecules, as well as the infiltration of inflammatory cells in young (3‐month old), middle‐aged (12‐month old) and elderly (18‐month old) T2DN and SD rats. We found that the expression of the adhesion molecules, ICAM‐1 and E‐selectin, were elevated in elderly T2DN (1.3‐fold and 1.8‐fold, respectively), and E‐selectin level was already higher in young T2DN (2.1‐fold) than in age‐matched SD rats. The number of infiltrating CD45+ leucocytes, CD3+ T cells, CD3−/CD4+ monocytes and CD68+ macrophages per gram of kidney were increased by 2.81±0.45, 2.82±0.44, 3.06±1.05, and 7.86±3.75 times, respectively, in elderly T2DN versus SD control. The rise in infiltrating inflammatory cells was correlated with elevated proteinuria (1144±202 in T2DN vs. 293±47 mg/day in SD) and plasma creatinine level (1.01±0.1 mg/dl in elderly T2DN vs. 0.50±0.02 mg/dl in SD), a greater degree of glomerular sclerosis and a 2‐fold increase in renal fibrosis in elderly T2DN rats versus age‐matched SD rats. These results indicate that the increased expression of adhesion molecules promotes infiltration of inflammatory cells, which is associated with the progression of DN and suggests that immune modulatory drugs may slow the progression of this disease. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .