title: Adenosine receptor expression in the development of renal fibrosis following ischemic injury.
abstract: Long-term renal allograft survival has not improved despite improvements in short term outcomes. Graft loss is characterized histologically by the development of interstitial fibrosis and tubular atrophy (IFTA). Mechanisms underlying the development of IFTA are multifactorial and include ischemia-reperfusion injury (IRI). Therapeutic options to reduce IFTA include management of immunologic causes, such as rejection, but despite these efforts IFTA can still occur and leads to the inexorable destruction of the transplanted kidney. The adenosine A2B receptor (A2BR) has recently been implicated in the development of renal fibrosis. We performed an observational study to examine the mRNA expression of the adenosine receptors after renal ischemia up to the development of renal fibrosis in a mouse model of unilateral IRI. A2BR was the only adenosine receptor that showed elevated expression following ischemia until the development of renal fibrosis 4 weeks after injury. At 2 weeks after ischemia, increased expression of the fibrotic markers transforming growth factor β and Collagen-1α was observed. Expression of hypoxia inducible factor 1α and endothelin-1, which lie downstream of A2BR activation and have been recognized to promote renal fibrosis, were also significantly up-regulated at 2 weeks after ischemia. Expression of fibrotic markers returned to baseline by 4 weeks after ischemia, indicating resolution of injury with the concurrent development of renal fibrosis and reduced renal function. Our data suggest that A2BR may be a therapeutic target in reducing the development of renal fibrosis after ischemia.
authors.affiliation: Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia; University of Melbourne, Victoria, Australia. Electronic address: veena.roberts@svhm.org.au.
authors.forename: V
authors.initials: V
authors.lastname: Roberts
authors.affiliation: Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.affiliation: Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia; University of Melbourne, Victoria, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Dwyer
authors.affiliation: Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowan
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: D018047:Receptors, Purinergic P1