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Autophagy has been implicated in age\u2010related diseases, including <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>. However, the molecular mechanisms underlying <jats:styled-content style=\"fixed-case\">hKLK<\/jats:styled-content>1\u2010mediated amelioration of age\u2010related <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content> via regulation of autophagy remains unknown. To explore the potential mechanism, male wild\u2010type Sprague\u2010Dawley rats (<jats:styled-content style=\"fixed-case\">WTR<\/jats:styled-content>) and transgenic rats harboring human <jats:italic><jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>) were bred till 4 or 18\u00a0months of age and divided into three groups: young <jats:styled-content style=\"fixed-case\">WTR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">yWTR<\/jats:styled-content>) as the control group, aged <jats:styled-content style=\"fixed-case\">WTR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">aWTR<\/jats:styled-content>) group, and aged <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">aTGR<\/jats:styled-content>) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure\/mean arterial pressure (<jats:styled-content style=\"fixed-case\">ICP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>) and total <jats:styled-content style=\"fixed-case\">ICP<\/jats:styled-content> were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that <jats:styled-content style=\"fixed-case\">hKLK<\/jats:styled-content>1 improved the impaired erectile function of aged rats. Compared to the <jats:styled-content style=\"fixed-case\">yWTR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">aTGR<\/jats:styled-content> groups, the <jats:styled-content style=\"fixed-case\">aWTR<\/jats:styled-content> group showed reduced smooth muscle\/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the <jats:styled-content style=\"fixed-case\">aWTR<\/jats:styled-content> group. <jats:styled-content style=\"fixed-case\">h<jats:italic>KLK<\/jats:italic><\/jats:styled-content><jats:italic>1<\/jats:italic> may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> pathway. These observations indicate that <jats:styled-content style=\"fixed-case\">h<jats:italic>KLK<\/jats:italic><\/jats:styled-content><jats:italic>1<\/jats:italic> is a potential gene therapy candidate for age\u2010related ED.<\/jats:p>","DOI":"10.1111\/andr.12512","type":"journal-article","created":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T12:37:47Z","timestamp":1529930267000},"page":"766-774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats"],"prefix":"10.1111","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2909-3912","authenticated-orcid":false,"given":"Z.","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8406-6549","authenticated-orcid":false,"given":"K.","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 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