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PPARgamma in Kidney Physiology and Pathophysiology.

Kiss-Tóth E, Roszer T - PPAR Res (2009)

Bottom Line: Synthetic PPARgamma ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli.Activation of PPARgamma has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis.Beside many beneficial effects, PPARgamma activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4012 Debrecen, Hungary.

ABSTRACT
Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) in kidney physiology has been explored recently. Synthetic PPARgamma ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPARgamma has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPARgamma activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPARgamma in the mesonephric distal collecting system, where PPARgamma positively regulates sodium and water resorbtion leading to the expansion of interstitial fluid volume. Recent studies indicate that PPARgamma is also involved in the normal kidney development, renal lipid metabolism, and activation of the renin-angiotensin system. In this paper, we give a synopsis of the current knowledge on PPARgamma functions in kidney phyisology and pathophysiology.

No MeSH data available.


Related in: MedlinePlus

Roles of PPARγ in the collecting system of the kidney. (a) Expressionof PPARγ is confined to the distalcollecting system (labeled with green) including connective tubules (cn) andcollective ducts (ct). (b) Hematoxylin and esoin stained cross-sections of thekidney medulla showing numerous collective ducts (ct). (c) Fluorescent PPARγ immunostaining in thesame region of the kidney. (d) Oil red-O stained sections of the distal tubules(dt) showing severe lipid accumulation in type 2 diabetic (db/db) mice. (e) Summaryof PPARγ functions in thecollective system.
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fig2: Roles of PPARγ in the collecting system of the kidney. (a) Expressionof PPARγ is confined to the distalcollecting system (labeled with green) including connective tubules (cn) andcollective ducts (ct). (b) Hematoxylin and esoin stained cross-sections of thekidney medulla showing numerous collective ducts (ct). (c) Fluorescent PPARγ immunostaining in thesame region of the kidney. (d) Oil red-O stained sections of the distal tubules(dt) showing severe lipid accumulation in type 2 diabetic (db/db) mice. (e) Summaryof PPARγ functions in thecollective system.

Mentions: Under physiologicalconditions, PPARγ is dominantly expressedin the collecting system of the mammalian urinary tract, including connectiverenal tubules and collecting ducts (Figure 2(a)). PPARγ is abundant in the inner renal medulla (Figures 2(b), 2(c)) and localized to the epithelial layer starting from medullary collecting ducts tothe urothelium of the ureter and the bladder [39–41]. PPARγ also occurs in renal medullaryinterstitial cells [39]. The PPARγ partner RXRα has a complimentarydistribution in the collecting ducts [42]. The connective tubules andcollective ducts are parts of the distal collecting system, where hormone-regulatedion exchange and water resorbtion takes place and provides the balance of interstitial fluid volume(Figure 2(e)). If aldosterone is present, sodium is resorbed and potassium issecreted. Sodium transport is followed by passive water resorbtion, therefore,this mechanism regulates the total electrolite and water volume in the body [43]. The epithelium of the collecting ducts is responsive to antidiuretic hormone. If the hormone is present, the epithelia becomes permeable to water. The distalcollecting system is, therefore, a major site of fluid volume regulation.


PPARgamma in Kidney Physiology and Pathophysiology.

Kiss-Tóth E, Roszer T - PPAR Res (2009)

Roles of PPARγ in the collecting system of the kidney. (a) Expressionof PPARγ is confined to the distalcollecting system (labeled with green) including connective tubules (cn) andcollective ducts (ct). (b) Hematoxylin and esoin stained cross-sections of thekidney medulla showing numerous collective ducts (ct). (c) Fluorescent PPARγ immunostaining in thesame region of the kidney. (d) Oil red-O stained sections of the distal tubules(dt) showing severe lipid accumulation in type 2 diabetic (db/db) mice. (e) Summaryof PPARγ functions in thecollective system.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654308&req=5

fig2: Roles of PPARγ in the collecting system of the kidney. (a) Expressionof PPARγ is confined to the distalcollecting system (labeled with green) including connective tubules (cn) andcollective ducts (ct). (b) Hematoxylin and esoin stained cross-sections of thekidney medulla showing numerous collective ducts (ct). (c) Fluorescent PPARγ immunostaining in thesame region of the kidney. (d) Oil red-O stained sections of the distal tubules(dt) showing severe lipid accumulation in type 2 diabetic (db/db) mice. (e) Summaryof PPARγ functions in thecollective system.
Mentions: Under physiologicalconditions, PPARγ is dominantly expressedin the collecting system of the mammalian urinary tract, including connectiverenal tubules and collecting ducts (Figure 2(a)). PPARγ is abundant in the inner renal medulla (Figures 2(b), 2(c)) and localized to the epithelial layer starting from medullary collecting ducts tothe urothelium of the ureter and the bladder [39–41]. PPARγ also occurs in renal medullaryinterstitial cells [39]. The PPARγ partner RXRα has a complimentarydistribution in the collecting ducts [42]. The connective tubules andcollective ducts are parts of the distal collecting system, where hormone-regulatedion exchange and water resorbtion takes place and provides the balance of interstitial fluid volume(Figure 2(e)). If aldosterone is present, sodium is resorbed and potassium issecreted. Sodium transport is followed by passive water resorbtion, therefore,this mechanism regulates the total electrolite and water volume in the body [43]. The epithelium of the collecting ducts is responsive to antidiuretic hormone. If the hormone is present, the epithelia becomes permeable to water. The distalcollecting system is, therefore, a major site of fluid volume regulation.

Bottom Line: Synthetic PPARgamma ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli.Activation of PPARgamma has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis.Beside many beneficial effects, PPARgamma activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4012 Debrecen, Hungary.

ABSTRACT
Involvement of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) in kidney physiology has been explored recently. Synthetic PPARgamma ligands can ameliorate the diabetic kidney disease through different mechanisms, involving inhibition of mesangial cell growth, reduction of mesangial matrix, and cytokine production of glomerular cells as well as promoting endothelial cell survival within the kidney glomeruli. Activation of PPARgamma has additional profibrotic consequences, which can contribute to wound healing in diabetic glomerulonephritis. Beside many beneficial effects, PPARgamma activation, however, can lead to severe water retention, a common side effect of thiazolidinedione therapy. This unwanted effect is due to the activation of PPARgamma in the mesonephric distal collecting system, where PPARgamma positively regulates sodium and water resorbtion leading to the expansion of interstitial fluid volume. Recent studies indicate that PPARgamma is also involved in the normal kidney development, renal lipid metabolism, and activation of the renin-angiotensin system. In this paper, we give a synopsis of the current knowledge on PPARgamma functions in kidney phyisology and pathophysiology.

No MeSH data available.


Related in: MedlinePlus