NDT Advance Access first published online on January 31, 2006
This version published online on February 22, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk084
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1 Nephrology Division, Assaf Harofeh Medical Center, Zerifin, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel
* To whom correspondence should be addressed. Background. The peroxisome proliferator activating nuclear receptors (PPAR) are activated in the context of inflammation, diabetes or normal pregnancy. Renal mesangial cells express PPAR- 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- 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- Conclusions. PPAR-
Received April 19, 2005
Accepted December 28, 2005
Original Article
Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats
Joshua Weissgarten 1 *,
Sylvia Berman 1,
Shai Efrati 1,
Micha Rapoport 2,
Zhan Averbukh 1,
and
Leonid Feldman 1
2 Department of Internal Medicine C, Assaf Harofeh Medical Center, Zerifin, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel
Joshua Weissgarten, E-mail: Weissgarten{at}asaf.health.gov.il
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Abstract
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-
1 production and nuclear factor
B (NF-
B) activation, in the situation of pregnancies, complicated or not with diabetes.
and NF-
B by specific ELISAs.
synthesis and significant decrease in the levels of NF-
B in mesangial cell nuclei were observed in all rosiglitazone treated groups.
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.![]()
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