This Month’s Highlights Hormones, Growth Factors, Cell Signaling, Cell Biology and Structure Stimulation of Proximal Tubule Cell Apoptosis by Albumin Bound Fatty Acids Mediated by Peroxisome Proliferator Activated Receptor

Hormones, Growth Factors, Cell Signaling, Cell Biology and Structure Stimulation of Proximal Tubule Cell Apoptosis by Albumin Bound Fatty Acids Mediated by Peroxisome Proliferator Activated Receptor Tubulotoxic Effects of Proteinuria: The Lipid Connection Is Strengthened. There is currently little doubt that sustained high-grade proteinuria has damaging renal effects. While the mechanisms involved continue to unfold, a link between proteinuria-induced tubular responses and interstitial inflammation has been documented. Several years ago, studies by Kees-Folts and Schreiner implicated protein-bound fatty acids in this cascade. In the study reported by Arici et al., an important relationship is documented between fatty acid–bearing albumin and tubular cell apoptosis. This effect appears to be mediated through activation of the peroxisome proliferatoractivated receptor gamma (PPAR(), which is a nuclear receptor that initiates gene transcription following ligand-dependent activation. Fatty acids are known to be PPAR( ligands. Since the important structural connection between tubulointerstitial disease and renal insufficiency is tubular destruction, the ability of albumin-bound fatty acids to activate PPAR( and initiate apoptosis in proximal tubular cells could represent an important pathophysiologic pathway. Furthermore, this study gives cause for some reflection about the consequences of pharmacologic use of PPAR( agonists in the treatment of type II diabetes. Much more clearly remains to be learned about the effects of PPAR( and its activation by various ligands within the kidney.