title: Aberrant expression of Wnt family contributes to the pathogenesis of diabetes-induced erectile dysfunction.
abstract: Diabetic erectile dysfunction (ED) has multiple causative factors, such as endothelial and smooth muscle dysfunction and cavernous fibrosis. Wnt signalling is essential for normal embryonic development and for tissue homeostasis in adults. Aberrant activation of Wnt family members has been implicated in tissue fibrosis and in angiogenesis. In this study, we investigated the differential expression of Wnts in the penises of mice with streptozotocin-induced diabetic ED. We also examined the effect of transforming growth factor-β1 (TGF-β1) on the expression of Wnts in primary cultured fibroblasts isolated from human tunica albuginea. Among the mouse and human Wnts tested, 16 mouse Wnts and 14 human Wnts were detected in the corpus cavernosum tissue of normal mice and in fibroblasts derived from human tunica albuginea respectively. We observed up-regulation of Wnt10b (known to be involved in tissue fibrosis) and down-regulation of Wnt16 (known to be involved in vasculogenesis and hematopoiesis), both in the diabetic condition in vivo and with treatment of fibroblasts with TGF-β1 in vitro. Wnt10b was mainly expressed in fibroblasts and Wnt16 was colocalized with smooth muscle cells in the corpus cavernosum tissue. Cavernous TGF-β1 protein expression and the degree of cavernous fibrosis determined by the ratio of collagen to smooth muscle content were significantly higher in diabetic mice than in controls. Cavernous endothelial content was significantly decreased by the diabetic condition. Overexpression of Wnt16 with plasmid vector accelerated tube formation in primary cultured mouse cavernous endothelial cells. However, down-regulation of Wnt10b with small interfering RNA did not decrease the production of extracellular matrix protein in human fibroblasts. This is the first report demonstrating the differential expression of Wnts in diabetic mouse penis. Aberrant Wnt expression might contribute to the pathogenesis of ED.
authors.affiliation: Department of Urology, National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Shin
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
authors.forename: M J
authors.initials: MJ
authors.lastname: Choi
authors.forename: J-M
authors.initials: JM
authors.lastname: Park
authors.forename: H-R
authors.initials: HR
authors.lastname: Jin
authors.forename: G N
authors.initials: GN
authors.lastname: Yin
authors.forename: J-K
authors.initials: JK
authors.lastname: Ryu
authors.forename: J-K
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D042783:Endothelial Cells; D007172:Erectile Dysfunction / Q000150:complications*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005355:Fibrosis; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000503:physiopathology; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000494:pharmacology*; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D016326:Extracellular Matrix Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C491119:WNT10B protein, human; C417262:WNT16 protein, human; D051153:Wnt Proteins; D013311:Streptozocin
keywords: Wnt; diabetes mellitus; erectile dysfunction; fibrosis; penis; transforming growth factor-beta1