BACKGROUND: Osteopontin is a macrophage chemotactic protein that has been pathogenetically linked to tissue injury in non-diabetic kidney disease. METHODS: To examine osteopontin expression and macrophage accumulation in diabetic nephropathy, diabetes was induced with streptozotocin (STZ) in the transgenic (mRen-2)27 rat, a rodent model which develops the structural and functional features of its human counterpart when rendered diabetic. Non-diabetic rats were randomly selected to receive either (STZ) or citrate buffer. Diabetic rats were further randomly selected to receive either the angiotensin-converting-enzyme inhibitor, perindopril (6 mg/kg/day), or the vehicle only for 12 weeks. RESULTS: When compared with control animals, diabetes was associated with a 10-fold increase in the gene expression of osteopontin. Increased transcript and immunostainable osteopontin were detected in tubular epithelial cells in association with extensive macrophage accumulation. Treatment with perindopril significantly ameliorated the overexpression of osteopontin in association with attenuation of macrophage accumulation. CONCLUSIONS: These findings suggest that osteopontin expression and macrophage accumulation may play a role in the tubulointerstitial injury in diabetic nephropathy, and that inhibition of osteopontin expression may be one of the mechanisms by which blockade of the renin-angiotensin system confers a renoprotective effect.
BACKGROUND:Osteopontin is a macrophage chemotactic protein that has been pathogenetically linked to tissue injury in non-diabetic kidney disease. METHODS: To examine osteopontin expression and macrophage accumulation in diabetic nephropathy, diabetes was induced with streptozotocin (STZ) in the transgenic (mRen-2)27 rat, a rodent model which develops the structural and functional features of its human counterpart when rendered diabetic. Non-diabeticrats were randomly selected to receive either (STZ) or citrate buffer. Diabeticrats were further randomly selected to receive either the angiotensin-converting-enzyme inhibitor, perindopril (6 mg/kg/day), or the vehicle only for 12 weeks. RESULTS: When compared with control animals, diabetes was associated with a 10-fold increase in the gene expression of osteopontin. Increased transcript and immunostainable osteopontin were detected in tubular epithelial cells in association with extensive macrophage accumulation. Treatment with perindopril significantly ameliorated the overexpression of osteopontin in association with attenuation of macrophage accumulation. CONCLUSIONS: These findings suggest that osteopontin expression and macrophage accumulation may play a role in the tubulointerstitial injury in diabetic nephropathy, and that inhibition of osteopontin expression may be one of the mechanisms by which blockade of the renin-angiotensin system confers a renoprotective effect.
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: Maria R Wing; Joseph M Devaney; Marshall M Joffe; Dawei Xie; Harold I Feldman; Elizabeth A Dominic; Nicolas J Guzman; Ali Ramezani; Katalin Susztak; James G Herman; Leslie Cope; Brennan Harmon; Bernard Kwabi-Addo; Heather Gordish-Dressman; Alan S Go; Jiang He; James P Lash; John W Kusek; Dominic S Raj Journal: Nephrol Dial Transplant Date: 2014-02-09 Impact factor: 5.992
Authors: Mi Young Lee; Myoung Sook Shim; Bo Hwan Kim; Soon Won Hong; Ran Choi; Eun Young Lee; Soo Min Nam; Gun Woo Kim; Jang Yel Shin; Young Goo Shin; Choon Hee Chung Journal: Diabetes Metab J Date: 2011-04-30 Impact factor: 5.376
Authors: Richard E Gilbert; Yuan Zhang; Spencer J Williams; Steven C Zammit; David I Stapleton; Alison J Cox; Henry Krum; Robyn Langham; Darren J Kelly Journal: PLoS One Date: 2012-10-10 Impact factor: 3.240