BACKGROUND: Rosiglitazone (Ros) has been shown to attenuate CXCL8 and ICAM-1 overexpression in renal tubular cells exposed to glycated albumin. The present study explores whether this can be translated into renoprotection in vivo. Uninephrectomized (Unx) type 2 diabetic db/db mice were chosen as a model of accelerated diabetic nephropathy. METHODS: Uninephrectomy was performed in 10-week-old db/db mice. They were then treated with vehicle, metformin or Ros for 8 weeks. RESULTS: Unx-db/db mice treated with Ros had lower serum creatinine and albuminuria, less severe glomerulosclerosis, tubulointerstitial injury, fewer infiltrating macrophages, and less proliferating nuclear antigen-positive tubular cells compared with mice treated with metformin that had a similar level of glycemic control and insulin resistance. In addition, Ros but not metformin attenuated renal cortical expression of CCL2, MIP-2, and ICAM-1 and inhibited p-STAT1 signal activation. Ros also increased glomerular nephrin expression. CONCLUSIONS: Our results delineated the biochemical and histologic characteristics of Unx-db/db mice and demonstrated the in vivo glucose-independent anti-inflammatory mechanisms of Ros in nephropathy of accelerated murine type 2 diabetes. 2010 S. Karger AG, Basel.
BACKGROUND:Rosiglitazone (Ros) has been shown to attenuate CXCL8 and ICAM-1 overexpression in renal tubular cells exposed to glycated albumin. The present study explores whether this can be translated into renoprotection in vivo. Uninephrectomized (Unx) type 2 diabetic db/db mice were chosen as a model of accelerated diabetic nephropathy. METHODS: Uninephrectomy was performed in 10-week-old db/db mice. They were then treated with vehicle, metformin or Ros for 8 weeks. RESULTS: Unx-db/db mice treated with Ros had lower serum creatinine and albuminuria, less severe glomerulosclerosis, tubulointerstitial injury, fewer infiltrating macrophages, and less proliferating nuclear antigen-positive tubular cells compared with mice treated with metformin that had a similar level of glycemic control and insulin resistance. In addition, Ros but not metformin attenuated renal cortical expression of CCL2, MIP-2, and ICAM-1 and inhibited p-STAT1 signal activation. Ros also increased glomerular nephrin expression. CONCLUSIONS: Our results delineated the biochemical and histologic characteristics of Unx-db/db mice and demonstrated the in vivo glucose-independent anti-inflammatory mechanisms of Ros in nephropathy of accelerated murine type 2 diabetes. 2010 S. Karger AG, Basel.
Authors: Miao Lin; Wai Han Yiu; Hao Jia Wu; Loretta Y Y Chan; Joseph C K Leung; Wo Shing Au; Kwok Wah Chan; Kar Neng Lai; Sydney C W Tang Journal: J Am Soc Nephrol Date: 2011-10-21 Impact factor: 10.121
Authors: Julia M Hum; Linda M O'Bryan; Arun K Tatiparthi; Erica L Clinkenbeard; Pu Ni; Martin S Cramer; Manoj Bhaskaran; Robert L Johnson; Jonathan M Wilson; Rosamund C Smith; Kenneth E White Journal: J Appl Physiol (1985) Date: 2019-01-03