Amelioration of anti-Thy1-glomerulonephritis by PPAR-γ agonism without increase of endothelial progenitor cell homing

Westerweel, Peter E.; Ouden, Krista den; Nguyen, Tri Q.; Goldschmeding, Roel; Joles, Jaap A.; Verhaar, Marianne C.

doi:10.1152/ajprenal.00019.2007

Cited by 7 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…41,42 Moreover, PPAR-g agonists can directly decrease glomerular TGF-b expression in both diabetic and nondiabetic model rats independent of its effect on glycemic control. 19,43 In vitro studies by Hong et al demonstrated that cytoplasmic phosphorylation of Smad2/3 that act to stimulate TGF-b-dependent nuclear events was unaffected by PPAR-g agonists, whereas PPAR-g agonists were found to inhibit Smad2/3 phosphorylation either through direct interaction with TGFbR-I or with nonphosphorylated Smads. 44 In this study, we demonstrated that a PPAR-g agonist significantly reduced the expression of both TGF-b1 and TGFbR-I at 7 days after UUO.…”

Section: Discussionmentioning

confidence: 99%

“…For example, activation of PPAR-g reduced glomerulosclerosis and apoptosis in various models including the 5/6 nephrectomy model, passive Heymann nephritis model, crescentic glomerulonephritis model, acute mesangial proliferative glomerulonephritis model, and renal ischemia-reperfusion injury model. [16][17][18][19][20][21] In vitro studies have focused on the effect on mesangial cells, where PPAR-g activation exerts antiproliferative and antifibrotic effects 22,23 via the modulation of transforming growth factor-b1 (TGF-b1)-mediated pathways. 24 TZDs also reduced the secretion of macrophage chemotactic protein-1 (MCP-1), a proinflammatory chemokine, in human HK-2 cells exposed to high concentrations of glucose.…”

mentioning

confidence: 99%

See 1 more Smart Citation

PPAR-γ agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-β

Kawai

Takao

Doi

et al. 2009

Laboratory Investigation

188

125

View full text Add to dashboard Cite

Thiazolidinediones (TZDs), synthetic peroxisome proliferator-activated receptor (PPAR)-g ligands, have a central role in insulin sensitization and adipogenesis. It has been reported that TZDs exert protective effects in both diabetic and nondiabetic models of renal disease, although the exact mechanism is not well understood. In particular, only a few studies have reported the renoprotective effects of TZDs in nondiabetic models of tubulointerstitial fibrosis and inflammation. Therefore, we investigated the anti-fibrotic and anti-inflammatory effects of the TZD troglitazone in the mouse model of unilateral ureteral obstruction (UUO). C57BL/6J mice underwent UUO and were studied after 3 and 7 days. Animals were divided into three groups and received control vehicle, troglitazone (150 mg/kg per day) or troglitazone (300 mg/kg per day) by gavage. Kidneys were harvested for morphological, mRNA and protein analysis. Reversetranscriptase-PCR was used to assess the expression of transforming growth factor-b1 (TGF-b1) and the TGF-b1 type I receptor (TGFbR-I). Protein expression was assessed by western blotting (TGFbR-I) and immunostaining (TGFbR-I, a-smooth muscle actin (a-SMA), type I collagen (collagen I), F4/80, and proliferating cell nuclear antigen (PCNA)). The expression of a-SMA, collagen I, and F4/80 was decreased in mice treated with troglitazone compared with the control group. The numbers of PCNA-positive interstitial cells were decreased in mice treated with troglitazone. TGF-b1 mRNA and TGFbR-I mRNA and protein expression were decreased in the group treated with troglitazone compared with the control group. The beneficial effects of troglitazone treatment were also dose dependent. PPAR-g agonist significantly reduced TGF-b and attenuated renal interstitial fibrosis and inflammation in the model of UUO.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PPAR-γ agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-β

Kawai

Takao

Doi

et al. 2009

Laboratory Investigation

188

125

View full text Add to dashboard Cite

show abstract

“…PGZ also stimulates the expression of TGF β and TGF β receptor [49], and thus initiates EPC conversion to the VSMC phenotype [50]: increased VSMC presence may stabilize the neovasculature and thus reduce angiogenesis. This may explain why PPAR γ agonists ameliorate glomerulonephritis in mouse model without increase in EPC homing [51]. …”

Section: Anti-angiogenic Effects Of Pparγ In Diverse Cell Types: Ementioning

confidence: 99%

PPARγ and Agonists against Cancer: Rational Design of Complementation Treatments

2008

View full text Add to dashboard Cite

PPARγ is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPARγ has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPARγ role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPARγ image as potential anticancer drug. Currently PPARγ is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPARγ and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPARγ regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPARγ agonists.

show abstract

“…They have recently been attracting considerable attention as renoprotective drugs useful for treating renal diseases that are associated with metabolic disorders and diabetic nephropathy 7,10–12 . There have also been a few reports indicating that PPAR‐γ agonists have renoprotective effects in cases of non‐metabolic renal disease, 13–15 and we recently demonstrated that Pio significantly reduced proteinuria and interstitial fibrosis in the SHC rat 7 . The experimental models analyzed in those few reports are associated with massive proteinuria, and the proteinuria was prominently decreased by treatment with a PPAR‐γ agonist.…”

Section: Discussionmentioning

confidence: 86%

Additive antifibrotic effects of pioglitazone and candesartan on experimental renal fibrosis in mice

Higashi¹,

Oda²,

Kushiyama³

et al. 2010

Nephrology

View full text Add to dashboard Cite

show abstract

Amelioration of anti-Thy1-glomerulonephritis by PPAR-γ agonism without increase of endothelial progenitor cell homing

Abstract: Westerweel PE, den Ouden K, Nguyen TQ, Goldschmeding R, Joles JA, Verhaar MC. Amelioration of anti-Thy1-glomerulonephritis by PPAR-␥ agonism without increase of endothelial progenitor cell homing.

Cited by 7 publications

References 31 publications

PPAR-γ agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-β

PPAR-γ agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-β

PPARγ and Agonists against Cancer: Rational Design of Complementation Treatments

Additive antifibrotic effects of pioglitazone and candesartan on experimental renal fibrosis in mice

Contact Info

Product

Resources

About