Open AccessG-CSF Prevents Progression of Diabetic Nephropathy in Rat
Author(s) -
Byung-Im So,
Yi-Sun Song,
Cheng-Hu Fang,
Jun-Young Park,
Yong-Gu Lee,
JeongHun Shin,
Hyuck Kim,
Kyung-Soo Kim
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0077048
Subject(s) - medicine , diabetic nephropathy , endocrinology , creatinine , glomerulosclerosis , transforming growth factor , glomerular basement membrane , saline , podocyte , growth factor , mesangial proliferative glomerulonephritis , membranous nephropathy , kidney , receptor , glomerulonephritis , proteinuria
Background The protective effects of granulocyte colony-stimulating factor (G-CSF) have been demonstrated in a variety of renal disease models. However, the influence of G-CSF on diabetic nephropathy (DN) remains to be examined. In this study, we investigated the effect of G-CSF on DN and its possible mechanisms in a rat model. Methods Otsuka Long-Evans Tokushima Fatty (OLETF) rats with early DN were administered G-CSF or saline intraperitoneally. Urine albumin creatinine ratio (UACR), creatinine clearance, mesangial matrix expansion, glomerular basement membrane (GBM) thickness, and podocyte foot process width (FPW) were measured. The levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and type IV collagen genes expression in kidney tissue were also evaluated. To elucidate the mechanisms underlying G-CSF effects, we also assessed the expression of G-CSF receptor (G-CSFR) in glomeruli as well as mobilization of bone marrow (BM) cells to glomeruli using sex-mismatched BM transplantation. Results After four weeks of treatment, UACR was lower in the G-CSF treatment group than in the saline group ( p <0.05), as were mesangial matrix expansion, GBM thickness, and FPW ( p <0.05). In addition, the expression of TGF-β1 and type IV collagen and IL-1β levels was lower in the G-CSF treatment group ( p <0.05). G-CSFR was not present in glomerular cells, and G-CSF treatment increased the number of BM-derived cells in glomeruli ( p <0.05). Conclusions G-CSF can prevent the progression of DN in OLETF rats and its effects may be due to mobilization of BM cells rather than being a direct effect.