title: CD39 overexpression does not attenuate renal fibrosis in the unilateral ureteric obstructive model of chronic kidney disease.
abstract: Chronic kidney disease has multiple etiologies, but its single, hallmark lesion is renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of ATP and increased CD39 activity on regulatory T cells (Treg) is protective in adriamycin-induced renal fibrosis. We examined the effect of overexpression of human CD39 on the development of renal fibrosis in the unilateral ureteric obstructive (UUO) model, a model widely used to study the molecular and cellular factors involved in renal fibrosis. Mice overexpressing human CD39 (CD39Tg) and their wild-type (WT) littermates were subjected to UUO; renal histology and messenger RNA (mRNA) levels of adenosine receptors and markers of renal fibrosis were examined up to 14 days after UUO. There were no differences between CD39Tg mice and WT mice in the development of renal fibrosis at days 3, 7, and 14 of UUO. Relative mRNA expression of the adenosine A2Areceptor and endothelin-1 were higher in CD39Tg than WT mice at day 7 post UUO, but there were no differences in markers of fibrosis. We conclude that human CD39 overexpression does not attenuate the development of renal fibrosis in the UUO model. The lack of protection by CD39 overexpression in the UUO model is multifactorial due to the different effects of adenosinergic receptors on the development of renal fibrosis.
authors: Immunology Research Centre, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia. Veena.ROBERTS@svha.org.au.|University of Melbourne, Victoria, Australia. Veena.ROBERTS@svha.org.au.
authors: Veena
authors: V
authors: Roberts
authors: Immunology Research Centre, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
authors: B
authors: B
authors: Lu
authors: Immunology Research Centre, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
authors: J
authors: J
authors: Chia
authors: Immunology Research Centre, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.|University of Melbourne, Victoria, Australia.
authors: P J
authors: PJ
authors: Cowan
authors: Immunology Research Centre, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.|University of Melbourne, Victoria, Australia.|School of Medicine, Faculty of Health, Deakin University, Victoria, Australia.
authors: K M
authors: KM
authors: Dwyer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001081:Apyrase / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D001081:Apyrase; C067869:CD39 antigen
keywords: Adenosine receptor; CD39; Renal fibrosis; Transforming growth factor-ß; Unilateral ureteric obstruction