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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2002 June;54(2):65-79

language: English

Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and urologic disease

Guan Y.

From the Division of Nephrology and Hypertension Department of Medicine Vanderbilt University Medical Center Nashville, TN, USA


Peroxisome proliferator-activated receptors (PPARs) are mem­bers of the nucle­ar hor­mone recep­tor super­fam­i­ly of ­ligand-acti­vat­ed tran­scrip­tion fac­tors. ­Three ­PPAR iso­forms, des­ig­nat­ed PPA­R-α, -β/δ, and -γ, ­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-α is pre­dom­i­nant­ly ­expressed in ­renal prox­i­mal ­tubules and medul­lary ­thick ascend­ing ­limbs. ­PPAR-γ is main­ly local­ized in ­renal medul­lary col­lect­ing ­duct ­with low­er expres­sion in ­renal glom­e­ru­li and ­renal micro­vas­cu­la­ture. ­Unlike PPA­R-α and -γ, ­PPAR-β/δ is ubiq­ui­tous­ly ­expres-sed 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-α ­plays a ­major ­role in trig­ger­ing fat­ty ­acid util­iza­tion and the adap­tive ­response to die­tary lip­ids in the kid­ney. ­PPAR-β/δ con­trib­utes to ­cell sur­vi­val of ­renal inter­sti­tial ­cell in medul­lary hyper­os­mal­ity. ­PPAR-γ 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.

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