{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:55:18Z","timestamp":1778752518729,"version":"3.51.4"},"reference-count":46,"publisher":"Portland Press Ltd.","issue":"20","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>Increased production of reactive oxygen species (ROS) and inflammation are major contributors to the development and progression of diabetes-associated erectile dysfunction (DMED). As an endogenous antioxidant and anti-inflammatory factor, the potential implication of pigment epithelium-derived factor (PEDF) in DMED has not been revealed. To assess the potential antioxidant and anti-inflammatory functions of PEDF in DMED, we first demonstrated that PEDF was significantly decreased at the levels of the mRNA and protein in the penis of diabetic rats compared with normal controls. To test the hypothesis that decreased the penile levels of PEDF are associated with oxidative stress and inflammation in DMED, an adenovirus expressing PEDF (Ad-PEDF) or the same titer of control virus (Ad-GFP) was intracavernously administered at 2 weeks after diabetic onset. After 6 weeks of treatment, we found that administration of Ad-PEDF could significantly increase erectile response to cavernosal nerve stimulation in the diabetic rats by restoring the endothelial NO synthase (eNOS), P-eNOS, and neuronal NO synthase (nNOS) protein levels to the standard levels represented in normal rats and by suppressing the levels of tumor necrosis factor-\u03b1 (TNF-\u03b1) and oxidative stress. In conclusion, the present data indicated that the antioxidant and anti-inflammatory potential of PEDF plays important role in restoring erectile function by the inhibition of oxidative stress and TNF-\u03b1 production.<\/jats:p>","DOI":"10.1042\/cs20180192","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T11:45:16Z","timestamp":1537357516000},"page":"2175-2188","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats"],"prefix":"10.1042","volume":"132","author":[{"given":"Hongjie","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina\u00a0M.","family":"Furdui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuling","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-nian","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"2019102623575017100_B1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jsxm.2015.12.019","article-title":"Segraves, definitions of sexual dysfunctions in women and men: a consensus statement from the fourth international consultation on sexual medicine 2015","volume":"13","author":"McCabe","year":"2016","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B2","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/S0022-5347(17)34871-1","article-title":"Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study","volume":"151","author":"Feldman","year":"1994","journal-title":"J. Urol."},{"key":"2019102623575017100_B3","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1111\/j.1743-6109.2008.01168.x","article-title":"Levy Erectile dysfunction in diabetes mellitus","volume":"6","author":"Malavige","year":"2009","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B4","first-page":"95","article-title":"Diabetes and sexual dysfunction: current perspectives","volume":"7","author":"Maiorino","year":"2014","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"2019102623575017100_B5","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/BF00251005","article-title":"The prevalence of diabetic impotence","volume":"18","author":"McCulloch","year":"1980","journal-title":"Diabetologia"},{"key":"2019102623575017100_B6","first-page":"1373","article-title":"Sexual functions in the diabetic male","volume":"11","author":"Fossati","year":"1982","journal-title":"Nouv. Presse Med."},{"key":"2019102623575017100_B7","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3109\/13685538.2015.1072154","article-title":"The effect of lifestyle modification and glycemic control on the efficiency of sildenafil citrate in patients with erectile dysfunction due to type-2 diabetes mellitus","volume":"18","author":"Kirilmaz","year":"2015","journal-title":"Aging Male"},{"key":"2019102623575017100_B8","doi-asserted-by":"publisher","first-page":"777","DOI":"10.2337\/diacare.26.3.777","article-title":"Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study","volume":"26","author":"Goldstein","year":"2003","journal-title":"Diabetes Care"},{"key":"2019102623575017100_B9","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.coph.2011.08.004","article-title":"PDE5 inhibitors: targeting erectile dysfunction in diabetics","volume":"11","author":"Francis","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"2019102623575017100_B10","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1111\/jcmm.12480","article-title":"Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats","volume":"19","author":"Wang","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"2019102623575017100_B11","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/nrurol.2016.23","article-title":"Molecular mechanisms associated with diabetic endothelial-erectile dysfunction","volume":"13","author":"Castela","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"2019102623575017100_B12","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/andr.12313","article-title":"(","volume":"5","author":"Musicki","year":"2017","journal-title":"Andrology"},{"key":"2019102623575017100_B13","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S0090-4295(97)00512-8","article-title":"Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS","volume":"50","author":"Seftel","year":"1997","journal-title":"Urology"},{"key":"2019102623575017100_B14","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jdiacomp.2010.03.003","article-title":"(","volume":"25","author":"Thorve","year":"2011","journal-title":"J. Diabetes Complication"},{"key":"2019102623575017100_B15","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s00210-013-0882-z","article-title":"Low nitric oxide bioavailability is associated with better responses to sildenafil in patients with erectile dysfunction","volume":"386","author":"Muniz","year":"2013","journal-title":"Naunyn Schmied. Arch. Pharmacol."},{"key":"2019102623575017100_B16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1743-6109.2008.01189.x","article-title":"TNF-alpha infusion impairs corpora cavernosa reactivity","volume":"6","author":"Carneiro","year":"2009","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B17","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1111\/j.1743-6109.2012.02739.x","article-title":"TNF-alpha, erectile dysfunction, and NADPH oxidase-mediated ROS generation in corpus cavernosum in high-fat diet\/streptozotocin- induced diabetic rats","volume":"9","author":"Long","year":"2012","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B18","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3349\/ymj.2003.44.2.236","article-title":"The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats","volume":"44","author":"Ryu","year":"2003","journal-title":"Yonsei Med. J."},{"key":"2019102623575017100_B19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1743-6109.2005.20228_1.x","article-title":"Superoxide anion production in the rat penis impairs erectile function in diabetes: influence of in vivo extracellular superoxide dismutase gene therapy","volume":"2","author":"Bivalacqua","year":"2005","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B20","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ejphar.2017.03.024","article-title":"Ethanol-induced erectile dysfunction and increased expression of pro-inflammatory proteins in the rat cavernosal smooth muscle are mediated by NADPH oxidase-derived reactive oxygen species","volume":"804","author":"Leite","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"2019102623575017100_B21","first-page":"6","article-title":"NADPH oxidase: recent evidence for its role in erectile dysfunction","volume":"10","author":"Jin","year":"2008","journal-title":"J. Androl."},{"key":"2019102623575017100_B22","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1111\/j.1743-6109.2011.02277.x","article-title":"Imbalanced low-grade inflammation and endothelial activation in patients with type 2 diabetes mellitus and erectile dysfunction","volume":"8","author":"Arana Rosainz Mde","year":"2011","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B23","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/ijir.2009.44","article-title":"The effect of anti-tumor necrosis factor agents on sexual dysfunction in male patients with ankylosing spondylitis: a pilot study","volume":"21","author":"Oh","year":"2009","journal-title":"Int. J. Impot. Res."},{"key":"2019102623575017100_B24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/j.1743-6109.2008.01029.x","article-title":"TNF-alpha knockout mice have increased corpora cavernosa relaxation","volume":"6","author":"Carneiro","year":"2009","journal-title":"J. Sex. Med."},{"key":"2019102623575017100_B25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1161\/01.RES.0000229685.37402.80","article-title":"Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome","volume":"99","author":"Picchi","year":"2006","journal-title":"Circ. Res."},{"key":"2019102623575017100_B26","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/jcb.22072","article-title":"Characterization of PEDF: a multi-functional serpin family protein","volume":"106","author":"Filleur","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"2019102623575017100_B27","doi-asserted-by":"publisher","first-page":"323","DOI":"10.196\/fj.05-4313fje","article-title":"Pigment epithelium-derived is an endogenous antiinflammatory factor","volume":"20","author":"Zhang","year":"2006","journal-title":"FASEB J."},{"key":"2019102623575017100_B28","doi-asserted-by":"publisher","first-page":"F1166","DOI":"10.1152\/ajprenal.00375.2007","article-title":"Anti-inflammatory effects of pigment epithelium-derived factor in diabetic nephropathy","volume":"294","author":"Wang","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"2019102623575017100_B29","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1002\/dmrr.1007","article-title":"Protective role of pigment epithelium-derived factor PEDF in early phase of experimental diabetic retinopathy","volume":"25","author":"Yoshida","year":"2009","journal-title":"Diabetes Metab. Res. Rev."},{"key":"2019102623575017100_B30","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.2353\/ajpath.2007.060838","article-title":"Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation","volume":"170","author":"Nakamura","journal-title":"Am. J. Pathol."},{"key":"2019102623575017100_B31","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1074\/mcp.M900286-MCP200","article-title":"Molecular targets for diabetes mellitus-associated erectile dysfunction","volume":"9","author":"Yohannes","year":"2010","journal-title":"Mol. Cell. Proteomics"},{"key":"2019102623575017100_B32","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s00441-016-2494-7","article-title":"Beneficial effect of PEDF-transfec ted ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model","volume":"366","author":"Lu","year":"2016","journal-title":"Cell Tissue Res."},{"key":"2019102623575017100_B33","doi-asserted-by":"publisher","first-page":"9121","DOI":"10.1073\/pnas.0400520101","article-title":"RhoA\/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction","volume":"101","author":"Bivalacqua","year":"2004","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2019102623575017100_B34","doi-asserted-by":"publisher","first-page":"243","DOI":"10.2337\/diabetes.54.1.243","article-title":"Decreased expression of pigment epithelium-derived factor is involved in the pathogenesis of diabetic nephropathy","volume":"54","author":"Wang","year":"2005","journal-title":"Diabetes"},{"key":"2019102623575017100_B35","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1111\/andr.12218","article-title":"Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats","volume":"4","author":"Musicki","year":"2016","journal-title":"Andrology"},{"key":"2019102623575017100_B36","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1038\/ijo.2012.223","article-title":"Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance","volume":"37","author":"Moreno-Navarrete","year":"2013","journal-title":"Int. J. Obes. (Lond.)"},{"key":"2019102623575017100_B37","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/aja.2012.22","article-title":"The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism","volume":"14","author":"Chen","year":"2012","journal-title":"Asian J. Androl."},{"key":"2019102623575017100_B38","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/ijo.2010.212","article-title":"Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells","volume":"35","author":"Famulla","year":"2011","journal-title":"Int. J. Obes. (Lond.)"},{"key":"2019102623575017100_B39","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1095\/biolreprod.112.103556","article-title":"Estrogen-Induced maldevelopment of the penis involves down-regulation of myosin heavy chain 11(MYH11) expression, a biomarker for smooth muscle cell differentiation","volume":"87","author":"Okumu","year":"2012","journal-title":"Biol Reprod"},{"key":"2019102623575017100_B40","doi-asserted-by":"publisher","first-page":"954","DOI":"10.2337\/db07-1524","article-title":"Protective effect of perindopril on diabetic retinopathy is associated with decreased vascular endothelial growth factor-to-pigment epithelium-derived factor ratio: involvement of a mitochondria-reactive oxygen species pathway","volume":"58","author":"Zheng","year":"2009","journal-title":"Diabetes"},{"key":"2019102623575017100_B41","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/ijir.2015.13","article-title":"Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat (ZDF\/fa\/fa)","volume":"27","author":"Tobll.","year":"2015","journal-title":"Int. J. Impot. Res."},{"key":"2019102623575017100_B42","first-page":"489","article-title":"[Ox-LDL down-regulates expression of pigment epithlium-derived factor in human umbilical vein endothelial cells]","volume":"66","author":"Liu","year":"2014","journal-title":"Sheng Li Xue Bao"},{"key":"2019102623575017100_B43","doi-asserted-by":"publisher","first-page":"411","DOI":"10.2174\/138945011605150504114041","article-title":"Pathophysiology of erectile dysfunction","volume":"16","author":"Matsui","year":"2015","journal-title":"Curr. Drug Target"},{"key":"2019102623575017100_B44","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.2337\/db05-1448","article-title":"Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for antifibrogenic activities","volume":"55","author":"Wang","year":"2006","journal-title":"Diabetes"},{"key":"2019102623575017100_B45","doi-asserted-by":"publisher","first-page":"e324","DOI":"10.1016\/S2214-109X(16)30367-9","article-title":"Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial","volume":"5","author":"Li","year":"2017","journal-title":"Lacet Glob. Health"},{"key":"2019102623575017100_B46","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.4088\/JCP.14r09179","article-title":"Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis","volume":"76","author":"Jimenez-Fernandez","year":"2015","journal-title":"J. Clin. Psychiatry"}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/portlandpress.com\/clinsci\/article-pdf\/132\/20\/2175\/450467\/cs-2018-0192.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/portlandpress.com\/clinsci\/article-pdf\/132\/20\/2175\/450467\/cs-2018-0192.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,27]],"date-time":"2019-10-27T03:57:56Z","timestamp":1572148676000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/132\/20\/2175\/72166\/Decreased-expression-of-pigment-epitheliumderived"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,19]]},"references-count":46,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2018,10,31]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20180192","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,19]]}}}