H-B Tan1, Y Feng, M Liu, Y-C Wu. 1. Second Hospital of Hebei Medical University, Department of Nephrology, Shijiazhuang, Hebei Province, PR China. huibintan@163.com
Abstract
BACKGROUND: Chronic allograft nephropathy (CAN) remains a challenge for transplant clinicians. Some novel intervention strategies may shed new light on its treatment. METHODS: An orthotopic kidney transplant model in Fisher-to-Lewis rats was used with administration of cyclosporine alone or in combination with FR167653 (30 mg/kg/d subcuntaneously) to recipients. We analyzed renal function and urinary protein excretion. Animals were sacrificed at 30 weeks posttransplantation for histological and immunohistochemical studies. RESULTS: Renal function among vehicle-treated rats deteriorated progressively with substantial proteinuria compared with FR167653-treated rats. FR167653 administration significantly prevented the morphlogical features of CAN and prolonged rat survivals. p38 mitogen-activated protein kinase (MAPK) expression was markedly reduced by FR167653 treatment. Meanwhile, transforming growth factor-beta1 and monocyte chemotactic protein-1 expression were significantly down-regulated among FR167653-treated hosts. CONCLUSION: p38 MAPK phosphorylation correlated with CAN progression and inhibition of p38 MAPK by FR167653 may provide a potent novel therapeutic target for its prevention.
BACKGROUND:Chronic allograft nephropathy (CAN) remains a challenge for transplant clinicians. Some novel intervention strategies may shed new light on its treatment. METHODS: An orthotopic kidney transplant model in Fisher-to-Lewis rats was used with administration of cyclosporine alone or in combination with FR167653 (30 mg/kg/d subcuntaneously) to recipients. We analyzed renal function and urinary protein excretion. Animals were sacrificed at 30 weeks posttransplantation for histological and immunohistochemical studies. RESULTS: Renal function among vehicle-treated rats deteriorated progressively with substantial proteinuria compared with FR167653-treated rats. FR167653 administration significantly prevented the morphlogical features of CAN and prolonged rat survivals. p38 mitogen-activated protein kinase (MAPK) expression was markedly reduced by FR167653 treatment. Meanwhile, transforming growth factor-beta1 and monocyte chemotactic protein-1 expression were significantly down-regulated among FR167653-treated hosts. CONCLUSION:p38 MAPK phosphorylation correlated with CAN progression and inhibition of p38 MAPK by FR167653 may provide a potent novel therapeutic target for its prevention.
Authors: Philip J O'Connell; Weijia Zhang; Madhav C Menon; Zhengzi Yi; Bernd Schröppel; Lorenzo Gallon; Yi Luan; Ivy A Rosales; Yongchao Ge; Bojan Losic; Caixia Xi; Christopher Woytovich; Karen L Keung; Chengguo Wei; Ilana Greene; Jessica Overbey; Emilia Bagiella; Nader Najafian; Milagros Samaniego; Arjang Djamali; Stephen I Alexander; Brian J Nankivell; Jeremy R Chapman; Rex Neal Smith; Robert Colvin; Barbara Murphy Journal: Lancet Date: 2016-07-22 Impact factor: 79.321
Authors: Amrita Dosanjh; Elizabeth Robison; Tony Mondala; Steven R Head; Daniel R Salomon; Sunil M Kurian Journal: BMC Genomics Date: 2013-04-23 Impact factor: 3.969