title: Preserved Erectile Function in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1.
abstract: Human tissue kallikrein 1 (hKLK1) has enormous potential for the protection of vasodilation and endothelial function in the cardiovascular system. Our previous study proved the decreased expression of kallikrein 1 in the corpus cavernosum (CC) of aged rats, but the role of kallikrein 1 in age-related erectile dysfunction remains unknown.
  
  
  
  To explore the effect and underlying mechanisms of hKLK1 on age-related erectile dysfunction.
  
  
  
  Male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 27 months of age, respectively, and divided into four groups: young WTR (yWTR) as the control, young TGR (yTGR), aged WTR (aWTR), and aged TGR (aTGR). Rats' erectile function was evaluated by the cavernous nerve electrostimulation method. Then, CCs were collected for verification of hKLK1 followed by measurement of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) and RhoA-Rho-kinase (ROCK) signaling activities. Masson trichrome staining and terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling assay were conducted to evaluate penile fibrosis and apoptosis.
  
  
  
  Erectile response, NO-cGMP and RhoA-ROCK pathway-related indices, ratio of smooth muscle to collagen, and apoptosis index.
  
  
  
  The hKLK1 alleviated the decrease of erectile function in the aWTR group. Endothelial NO synthase (eNOS) and phospho-eNOS(Ser1177) expressions, NO synthase activity, and NO and cGMP levels were decreased, whereas phospho-eNOS(Thr495), L-type Ca(2+) channel, RhoA, ROCK1, ROCK2, and transforming growth factor β1 proteins were increased in the CCs of the aWTR group compared with the control yWTR group. These changes were obviously mitigated in the aTGR group. Moreover, hKLK1 prevented the sharp decrease of the ratio of smooth muscle to collagen and the increase of the apoptosis index in the CCs of the aWTR group.
  
  
  
  These results suggest that hKLK1 could play a preventive role in age-related erectile dysfunction by activation of the NO-cGMP pathway and inhibition of the RhoA-ROCK pathway and by antitissue fibrotic and apoptotic effects.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhuan
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ruibao
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Cui
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shaogang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: jhliu@tjh.tjmu.edu.cn.
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D007172:Erectile Dysfunction / Q000378:metabolism* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D054461:Lim Kinases / Q000378:metabolism*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D020840:Tissue Kallikreins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D052250:Nitric Oxide Synthase Type III; D054461:Lim Kinases; D054460:rho-Associated Kinases; D020840:Tissue Kallikreins; D006152:Cyclic GMP
keywords: Aged; Cyclic Guanosine Monophosphate; Erectile Dysfunction; Fibrosis; Gene Therapy; Kallikrein 1