Trans-Species Comparison of PPAR and RXR Expression by Rat and Human Urothelial Tissues

TY - JOUR

T1 - Trans-Species Comparison of PPAR and RXR Expression by Rat and Human Urothelial Tissues

AU - Chopra, Bikramjit

AU - Hinley, Jennifer

AU - Oleksiewicz, Martin B.

AU - Southgate, Jennifer

PY - 2008/4

Y1 - 2008/4

N2 - Because some investigational peroxisome proliferator-activated receptors (PPAR) agonists cause tumors in the lower urinary tract of rats, we compared normal human and rat urothelium in terms of PPAR and retinoid X receptor (RXR) expression and proliferation-associated phenotypes. In situ, few human but most rat urothelial cells were Ki67 positive, indicating fundamental differences in cell cycle control. Rat and human urothelia expressed all 3 PPAR and the RXR alpha and RXR beta isoforms in a predominantly nuclear localization, indicating that they may be biologically active. However, immunolocalization differences were observed between species. First, whereas PPAR alpha and PPAR beta/delta were expressed throughout the human bladder or ureteric urothelium, in the rat urothelium PPAR alpha was primarily, and PPAR beta/delta exclusively, restricted to superficial cells. Second, RXR beta was restricted to intermediate and superficial layers of the human urothelium but tended to be absent from the rat superficial cells. Third, PPAR gamma expression was present throughout the urothelia of both species but was most intense in the superficial human urothelium. Species differences were also observed in the expression of PPAR and RXR isoforms between cultured rat and human urothelial cells and in the smooth muscle. Our findings highlight the unique coexpression of multiple PPAR and RXR isoforms by urothelium and suggest that species differences in PPAR function between rat and human urothelia may be explored in an in vitro setting.

AB - Because some investigational peroxisome proliferator-activated receptors (PPAR) agonists cause tumors in the lower urinary tract of rats, we compared normal human and rat urothelium in terms of PPAR and retinoid X receptor (RXR) expression and proliferation-associated phenotypes. In situ, few human but most rat urothelial cells were Ki67 positive, indicating fundamental differences in cell cycle control. Rat and human urothelia expressed all 3 PPAR and the RXR alpha and RXR beta isoforms in a predominantly nuclear localization, indicating that they may be biologically active. However, immunolocalization differences were observed between species. First, whereas PPAR alpha and PPAR beta/delta were expressed throughout the human bladder or ureteric urothelium, in the rat urothelium PPAR alpha was primarily, and PPAR beta/delta exclusively, restricted to superficial cells. Second, RXR beta was restricted to intermediate and superficial layers of the human urothelium but tended to be absent from the rat superficial cells. Third, PPAR gamma expression was present throughout the urothelia of both species but was most intense in the superficial human urothelium. Species differences were also observed in the expression of PPAR and RXR isoforms between cultured rat and human urothelial cells and in the smooth muscle. Our findings highlight the unique coexpression of multiple PPAR and RXR isoforms by urothelium and suggest that species differences in PPAR function between rat and human urothelia may be explored in an in vitro setting.

KW - bladder

KW - Ki67

KW - lower urinary tract

KW - PPAR

KW - RXR

KW - urothelium

KW - ACTIVATED-RECEPTOR-ALPHA

KW - MUSCLE-CELL PROLIFERATION

KW - URINARY-BLADDER

KW - ALPHA/GAMMA AGONIST

KW - INSULIN SENSITIVITY

KW - GLYCEMIC CONTROL

KW - IN-VITRO

KW - ZDF RATS

KW - GAMMA

KW - DIFFERENTIATION

UR - http://www.scopus.com/inward/record.url?scp=48549093258&partnerID=8YFLogxK

U2 - 10.1177/0192623308315672

DO - 10.1177/0192623308315672

M3 - Article

C2 - 18441255

VL - 36

SP - 485

EP - 495

JO - Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie

JF - Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie

IS - 3

ER -