title: Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats.
abstract: BACKGROUND
  Erectile dysfunction (ED) is a major health problem. It is known that diabetic patients are more refractory to common treatments for ED.
  
  
  OBJECTIVE
  To explore the better treatment for ED, we examined the effects of adipose-derived stem cells (ASC) on ED using a diabetic rat model. We also analyzed the cytokines produced by ASC and implicated in ASC-induced restoration of erectile function.
  
  
  METHODS
  Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. ASC or adenoviruses were injected into the penis 6 weeks after STZ administration. Erectile function, penile histology and protein expression were analyzed 4 weeks after the injection of ASC or adenoviruses.
  
  
  METHODS
  Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. The morphology of the penis was analyzed by Elastica van Gieson stain and immunohistochemistry. The expression of proteins specific for vascular endothelial cells (VEC) was assessed by Western blot analysis.
  
  
  RESULTS
  ASC restored erectile function especially when they were cultured in medium containing growth factors for VEC. This restoration was associated with improvement in the histology of the cavernous body, and increased expression of VEC markers such as VE-cadherin and endothelial nitric oxide synthase (eNOS). When the expression of adrenomedullin (AM), a vasoactive peptide originally isolated from human pheochromocytoma tissue, was knocked down, the effect of ASC on ED was significantly diminished. Knockdown of AM was associated with decreased expressions of VE-cadherin and eNOS. Furthermore, overexpression of AM induced by adenovirus infection significantly improved erectile function in these diabetic rats. Overexpression of AM was associated with increased expressions of VE-cadherin and eNOS.
  
  
  CONCLUSIONS
  These results suggested that ASC have the potentials to restore erectile function and that AM produced by ASC plays a major role in the restoration of erectile function.
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kumano
authors.forename: Akira
authors.initials: A
authors.lastname: Nomiya
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D053607:Adrenomedullin / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007172:Erectile Dysfunction / Q000503:physiopathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D010410:Penile Erection / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D053607:Adrenomedullin