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PPARgamma ligands attenuate mesangial contractile dysfunction in high glucose
Maki Ueta1, Masanori Wakisaka, Tetsuro Ago
1Department of Medicine and Clinical Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Kidney International
|February 12, 2004
Summary
High glucose reduces peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) in mesangial cells, impairing function. PPARgamma ligands restore PPARgamma1 levels and contractile response, suggesting therapeutic potential.
Area of Science:
- Cell Biology
- Molecular Biology
- Renal Physiology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a role in mesangial cell function.
- High glucose conditions impact PPARgamma expression and cellular responses in the kidney.
Purpose of the Study:
- To investigate the regulation of PPARgamma1 in mesangial cells under high glucose.
- To determine the effects of PPARgamma ligands on cell phenotype and contractile function.
Main Methods:
- Cultured rat mesangial cells were exposed to high glucose (20 mmol/L).
- Expression of PPARgamma1 (protein and mRNA) and alpha-smooth muscle actin (alphaSMA) was analyzed.
- Cellular contraction in response to angiotensin II was measured.
- Involvement of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways was assessed.
Main Results:
- High glucose and PKC activation decreased PPARgamma1 expression, an effect inhibited by PD98059 (MAPK inhibitor).
- Reduced PPARgamma1 correlated with increased alphaSMA and impaired angiotensin II-induced contraction.
- PPARgamma ligands reversed these changes, restoring PPARgamma1 levels and contractile function.
Conclusions:
- MAPK signaling suppresses PPARgamma1 transcription.
- Downregulation of PPARgamma1 in high glucose leads to mesangial cell phenotypic changes and contractile dysfunction.
- PPARgamma ligands can ameliorate high glucose-induced damage in mesangial cells.