BACKGROUND: The peroxisome proliferator activating nuclear receptors (PPAR) are activated in the context of inflammation, diabetes or normal pregnancy. Renal mesangial cells express PPAR-gamma which upon activation are capable of exerting anti-inflammatory effects. We investigated the effect of in vivo treatment by rosiglitazone on angiotensin II (A-II) stimulated manifestations of inflammation in cultured renal mesangial cells, such as proliferation, apoptosis, TGF-beta1 production and nuclear factor kappaB (NF-kappaB) activation, in the situation of pregnancies, complicated or not with diabetes. METHODS: Mesangial cells were isolated from the following groups, receiving or not 5 mg/kg rosiglitazone for 20 days: normal controls, normal pregnant rats, those with streptozotocine induced diabetes and pregnant diabetic rats. Proliferation was assessed by 3H-thymidine incorporation. Apoptosis was evaluated by TUNEL assay. AT-1/AT-2 receptor density was assessed by 125I-AT-2 labelling, TGF-beta and NF-kappaB by specific ELISAs. RESULTS: Rosiglitazone pretreatment resulted in significantly decreased proliferation, apoptosis and reduced responsiveness to A-II stimulation in cultures from controls, pregnant rats and non-pregnant diabetic animals. In the pregnant diabetic group which received rosiglitazone prior to sacrifice, responsiveness to A-II was completely blunted. Moderate attenuation of TGF-beta synthesis and significant decrease in the levels of NF-kappaB in mesangial cell nuclei were observed in all rosiglitazone treated groups. CONCLUSIONS: PPAR-gamma activation by rosiglitazone resulted in decreased manifestation of inflammatory hallmarks, including inhibition of mesangial cell proliferation, downregulation of apoptosis and blunted responsiveness to A-II. These anti-inflammatory renoprotective effects were maximally expressed in cultures from pregnant diabetic animals. The therapeutic relevance of these observations is a matter of further investigations.
BACKGROUND: The peroxisome proliferator activating nuclear receptors (PPAR) are activated in the context of inflammation, diabetes or normal pregnancy. Renal mesangial cells express PPAR-gamma which upon activation are capable of exerting anti-inflammatory effects. We investigated the effect of in vivo treatment by rosiglitazone on angiotensin II (A-II) stimulated manifestations of inflammation in cultured renal mesangial cells, such as proliferation, apoptosis, TGF-beta1 production and nuclear factor kappaB (NF-kappaB) activation, in the situation of pregnancies, complicated or not with diabetes. METHODS: Mesangial cells were isolated from the following groups, receiving or not 5 mg/kg rosiglitazone for 20 days: normal controls, normal pregnant rats, those with streptozotocine induced diabetes and pregnant diabeticrats. Proliferation was assessed by 3H-thymidine incorporation. Apoptosis was evaluated by TUNEL assay. AT-1/AT-2 receptor density was assessed by 125I-AT-2 labelling, TGF-beta and NF-kappaB by specific ELISAs. RESULTS:Rosiglitazone pretreatment resulted in significantly decreased proliferation, apoptosis and reduced responsiveness to A-II stimulation in cultures from controls, pregnant rats and non-pregnant diabetic animals. In the pregnant diabetic group which received rosiglitazone prior to sacrifice, responsiveness to A-II was completely blunted. Moderate attenuation of TGF-beta synthesis and significant decrease in the levels of NF-kappaB in mesangial cell nuclei were observed in all rosiglitazone treated groups. CONCLUSIONS:PPAR-gamma activation by rosiglitazone resulted in decreased manifestation of inflammatory hallmarks, including inhibition of mesangial cell proliferation, downregulation of apoptosis and blunted responsiveness to A-II. These anti-inflammatory renoprotective effects were maximally expressed in cultures from pregnant diabetic animals. The therapeutic relevance of these observations is a matter of further investigations.
Authors: Melanie S Joy; Debbie S Gipson; Mary Dike; Leslie Powell; Amber Thompson; Suzanne Vento; Allison Eddy; Agnes B Fogo; Jeffrey B Kopp; Daniel Cattran; Howard Trachtman Journal: Clin J Am Soc Nephrol Date: 2008-12-10 Impact factor: 8.237
Authors: Jami E Milam; Venkateshwar G Keshamouni; Sem H Phan; Biao Hu; Srinivasa R Gangireddy; Cory M Hogaboam; Theodore J Standiford; Victor J Thannickal; Raju C Reddy Journal: Am J Physiol Lung Cell Mol Physiol Date: 2007-12-27 Impact factor: 5.464
Authors: Melinda T Coughlan; David R Thorburn; Sally A Penfold; Adrienne Laskowski; Brooke E Harcourt; Karly C Sourris; Adeline L Y Tan; Kei Fukami; Vicki Thallas-Bonke; Peter P Nawroth; Michael Brownlee; Angelika Bierhaus; Mark E Cooper; Josephine M Forbes Journal: J Am Soc Nephrol Date: 2009-01-21 Impact factor: 10.121