Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and urologic disease.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Three PPAR isoforms, designated PPAR-alpha, beta/delta and -gamma, have been identified and were initially investigated in the tissues along urinary tract because of their known role in regulating lipid-activated gene transcription, lipid metabolism, inflammation and cell proliferation and differentiation. Gene distribution studies suggested that 3 PPAR isoforms are differentially expressed in the kidney. PPAR-alpha is predominantly expressed in renal proximal tubules and medullary thick ascending limbs. PPAR-gamma is mainly localized in renal medullary collecting duct with lower expression in renal glomeruli and renal microvasculature. Unlike PPAR-alpha and -gamma, PPAR-beta/delta is ubiquitously expressed in every segment along the nephron. In ureter and urinary bladder, all PPAR isoforms are mainly localized in urothelium of ureter and bladder. The emerging data have suggested physiological and pathophysiological roles of PPARs in tissues along urinary tract. PPAR-alpha plays a major role in triggering fatty acid utilization and the adaptive response to dietary lipids in the kidney. PPAR-beta/delta contributes to cell survival of renal interstitial cell in medullary hyperosmality. PPAR-gamma is involved in regulating renal hemodynamic and water and sodium transport. Furthermore, it also participates in the pathogenesis of glomerulopathy, antidiabetic thiazolidinedione-related water and sodium retention and renal, bladder and prostate carcinomas. PPARs may serve as potential therapeutic targets for certain diseases along urinary tract including glomerulosclerosis, diabetic nephropathy and kidney, prostate and bladder tumors.
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2372, USA. youfei.guan@mcmail.vanderbilt.edu
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D004041:Dietary Fats / Q000493:pharmacokinetics; D019281:Dimerization; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D009928:Organ Specificity; D020025:Peroxisome Proliferators / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D014551:Urinary Tract / Q000378:metabolism; D014570:Urologic Diseases / Q000188:drug therapy* / Q000378:metabolism; D014571:Urologic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004041:Dietary Fats; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D020025:Peroxisome Proliferators; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors