PMID- 27992968 OWN - NLM STAT- MEDLINE DCOM- 20171207 LR - 20220321 IS - 2047-2927 (Electronic) IS - 2047-2919 (Linking) VI - 5 IP - 2 DP - 2017 Mar TI - Establishment of in vitro model of erectile dysfunction for the study of high-glucose-induced angiopathy and neuropathy. PG - 327-335 LID - 10.1111/andr.12307 [doi] AB - Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes-induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high-glucose-induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal-glucose (5 mmoL) or high-glucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high-glucose condition. To study cellular interaction between MCECs and MCPs, co-culture systems including indirect contact, indirect non-contact, and direct mixed co-culture system, were established. We observed impaired tube formation and increased permeability in MCECs-MCPs co-culture exposed to high-glucose condition. To evaluate the effect of high-glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS-positive nerve fibers were significantly lower in MPG tissues exposed to the high-glucose condition than in the tissues exposed to the normal-glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for drug discovery and development of novel therapeutic modalities for erectile dysfunction. CI - (c) 2016 American Society of Andrology and European Academy of Andrology. FAU - Yin, G N AU - Yin GN AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Park, S-H AU - Park SH AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Song, K-M AU - Song KM AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Limanjaya, A AU - Limanjaya A AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Ghatak, K AU - Ghatak K AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Minh, N N AU - Minh NN AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Ock, J AU - Ock J AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. FAU - Ryu, J-K AU - Ryu JK AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. AD - Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Korea. FAU - Suh, J-K AU - Suh JK AD - National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161219 PL - England TA - Andrology JT - Andrology JID - 101585129 RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 119978-18-6 (matrigel) RN - 9007-34-5 (Collagen) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Coculture Techniques MH - Collagen MH - Diabetic Angiopathies/*physiopathology MH - Diabetic Neuropathies/*physiopathology MH - Disease Models, Animal MH - Drug Combinations MH - Endothelial Cells/*drug effects MH - Erectile Dysfunction/*physiopathology MH - Glucose/*pharmacology MH - Laminin MH - Male MH - Mice MH - Pericytes/*drug effects MH - Permeability MH - Proteoglycans OTO - NOTNLM OT - angiopathy OT - erectile dysfunction OT - neuropathy EDAT- 2016/12/20 06:00 MHDA- 2017/12/08 06:00 CRDT- 2016/12/20 06:00 PHST- 2016/06/29 00:00 [received] PHST- 2016/10/16 00:00 [revised] PHST- 2016/11/02 00:00 [accepted] PHST- 2016/12/20 06:00 [pubmed] PHST- 2017/12/08 06:00 [medline] PHST- 2016/12/20 06:00 [entrez] AID - 10.1111/andr.12307 [doi] PST - ppublish SO - Andrology. 2017 Mar;5(2):327-335. doi: 10.1111/andr.12307. Epub 2016 Dec 19.