REDUCED EXPRESSION OF A NOVEL PEPTIDE, PROSTACYCLIN-STIMULATING FACTOR, IN THE KIDNEYS OF STREPTOZOTOCIN-INDUCED DIABETIC RATS

Prostacyclin (PGI(2)) produced by vascular endothelial cells (ECs) is a potent vasoactive prostanoid involved in maintenance of vessel wall homeostasis. Reduced PGI(2) synthesis by vascular ECs could be a mecha nism of pathogenesis in the development of vascular lesions such as di abetic angiopathy. Recently, we purified and cloned a novel bioactive peptide, PGI(2)-stimulating factor (PSF), which stimulates PGI(2) prod uction by vascular ECs. PSF may act on vascular ECs in a paracrine and /or autocrine fashion to regulate PGI(2) synthesis. Decreased PSF prod uction in the vessel wall may result in an imbalance of prostanoid syn thesis, leading to the development of vascular lesions such as diabeti c angiopathy. Our immunohistochemical study demonstrated that PSF is l ocated in vascular resident cells such as vascular smooth muscle cells (SMCs) and ECs, as well as in bronchial SMCs. Moreover, PSF mRNA was found to be expressed in various tissues in Wistar rats, particularly in the kidneys and lungs. The present study demonstrated that streptoz otocin (STZ)-induced diabetic rats showed less PSF mRNA expression in the kidneys (PSF mRNA/28S rRNA ratio; STZ versus control; 1.7 +/- 0.2 versus 2.5 +/- 0.2, y < 0.05) and reduced immunohistochemical staining for PSF in arteries in the kidney. However, in the lungs, there were no changes in tissue PSF mRNA expression (STZ versus control; 10.9 +/- 0.9 versus 11.5 +/- 1.0, NS) or in the extent of PSF staining in bron chial SMCs of STZ-induced diabetic rats. These findings suggest that d ecreased expression of PSF in renal vessels of STZ-induced diabetic ra ts may cause an imbalance of prostanoid synthesis, leading to the deve lopment and progression of vascular damage in the kidney. (C) 1998 Els evier Science Inc.