The effects of indomethacin on angiogenic factors mRNA expression in renal cortex of healthy rats.
Indomethacin is a nonsteroidal anti-inflammatory drug used frequently to control chronic or temporary pain. In the kidney, indomethacin decreases medullary and cortical perfusion, resulting in hypoxia. Kidney hypoxia has many effects, including changes in gene expression, and is a strong stimulus for angiogenesis. Other angiogenic factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), transforming growth factor beta 1 (TGFbeta1), and platelet-derived growth factor (PDGF). Our goal was to examine the influence of indomethacin on mRNA expression of these factors and their selected receptors in the renal cortex of healthy rats. Groups of 8 healthy, male, six-week-old Wistar rats received either indomethacin (5 mg/kg/day) or placebo orally for three months. RNA from renal cortex biopsies was analyzed by real-time polymerase chain reaction to quantify the mRNA levels of each cytokine. We observed significantly higher mRNA levels for VEGF (1.73-fold), FGF-2 (5.6-fold) and TGFbeta receptor III (2.93-fold), PDGF receptor alpha (2.93-fold) and receptor beta (2.91-fold) in rats receiving indomethacin compared to rats given placebo (p < 0.05). Amounts of mRNA for TGFbeta1, PDGF, FGF receptors 1 and 2 and TGFbeta receptor I did not differ between analysed groups. Our data indicates that indomethacin may regulate the expression of potent angiogenic factors VEGF and FGF-2.
Mucha
K
K
Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Poland.
Foroncewicz
B
B
Koziak
K
K
Czarkowska-Paczek
B
B
Paczek
L
L
D042501:Angiogenic Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042501:Angiogenic Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; C071736:betaglycan; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D007213:Indomethacin