title: Association between endothelin-1 and collagen deposition in db/db diabetic mouse kidneys.
abstract: Endothelin-1 has been implicated in diabetic kidney injury, but there are few firm data establishing the temporal and spatial expression of kidney endothelin-1 in diabetes. We performed an immunohistochemical and histopathological analysis to determine endothelin-1 peptide expression in the kidneys of diabetic db/db mice and non-diabetic db/m controls. Diabetic mice were studied at 8 weeks, before histological damage is evident, and again at 16 weeks, when significant glomerular injury has occurred. Urinary endothelin-1 was 6.2- and 3.6-fold higher in 8- and 16-week diabetic mice compared to age-matched controls (P<0.01 db/db vs. db/m). Compared to non-diabetic kidneys, immunoreactive endothelin-1 was first elevated 2.5-fold (P=0.02) in the tubulointerstitial compartment at 8-week and remained high (3.8-fold, P<0.01) at 16 weeks. In contrast, glomerular endothelin-1 was elevated 3.2-fold (P=0.03) only in 16-week diabetic mice. Glomerular and tubulointerstitial endothelin-1 were unchanged in 8- and 16-week non-diabetic mice. Elevated endothelin-1 in diabetic mice associated temporally and spatially with collagen deposition, especially in the tubulointerstitial compartment. The localization of kidney endothelin-1 is consistent with a role for this peptide in renal fibrogenesis. These results also highlight the potential role of ET-1 in the pathogenesis of early tubulointerstitial changes in diabetes.
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
authors.forename: Rangnath
authors.initials: R
authors.lastname: Mishra
authors.forename: Steven N
authors.initials: SN
authors.lastname: Emancipator
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simonson
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice
chemical_list: D019332:Endothelin-1; D003094:Collagen