PMID- 30618416 OWN - NLM STAT- MEDLINE DCOM- 20200805 LR - 20200805 IS - 1745-7262 (Electronic) IS - 1008-682X (Print) IS - 1008-682X (Linking) VI - 21 IP - 5 DP - 2019 Sep-Oct TI - Human tissue kallikrein-1 protects against the development of erectile dysfunction in a rat model of hyperhomocysteinemia. PG - 508-515 LID - 10.4103/aja.aja_111_18 [doi] AB - The aim of this study was to investigate the mechanism by which a diet inducing high hyperhomocysteinemia (HHcy) leads to the deterioration of erectile function in rats and whether this is inhibited by expression of the human tissue kallikrein-1 (hKLK1) gene. We established a rat model of HHcy by feeding methionine (Met)-rich diets to male Sprague-Dawley (SD) rats. Male wild-type SD rats (WTRs) and transgenic rats harboring the hKLK1 gene (TGRs) were fed a normal diet until 10 weeks of age. Then, 30 WTRs were randomly divided into three groups as follows: the control (n = 10) group, the low-dose (4% Met, n = 10) group, and the high-dose (7% Met, n = 10) group. Another 10 age-matched TGRs were fed the high-dose diet and designated as the TGR+7% Met group. After 30 days, in all four groups, erectile function was measured and penile tissues were harvested to determine oxidative stress, endothelial cell content, and penis fibrosis. Compared with the 7% Met group, the TGR+7% Met group showed diminished HHcy-induced erectile dysfunction (ED), indicating the improvement caused by hKLK1. Regarding corpus cavernosum endothelial cells, hKLK1 preserved endothelial cell-cell junctions and endothelial cell content, and activated protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) signaling. Fibrosis assessment indicated that hKLK1 preserved normal penis structure by inhibiting apoptosis in the corpus cavernosum smooth muscle cells. Taken together, these findings showed that oxidative stress, impaired corpus cavernosum endothelial cells, and severe penis fibrosis were involved in the induction of ED by HHcy in rats, whereas hKLK1 preserved erectile function by inhibiting these pathophysiological changes. FAU - Cui, Kai AU - Cui K AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Luan, Yang AU - Luan Y AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Tang, Zhe AU - Tang Z AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Li, Chuan-Chang AU - Li CC AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Tao AU - Wang T AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Shao-Gang AU - Wang SG AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Chen, Zhong AU - Chen Z AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Liu, Ji-Hong AU - Liu JH AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Asian J Androl JT - Asian journal of andrology JID - 100942132 RN - AE28F7PNPL (Methionine) RN - EC 3.4.21.35 (Tissue Kallikreins) SB - IM MH - Animals MH - Apoptosis MH - Diet MH - Endothelial Cells MH - Erectile Dysfunction/*etiology/pathology/*prevention & control MH - Fibrosis MH - Humans MH - Hyperhomocysteinemia/chemically induced/*complications MH - Male MH - Methionine MH - Oxidative Stress MH - Penis/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Rats, Transgenic MH - Signal Transduction/genetics MH - Tissue Kallikreins/*genetics PMC - PMC6732897 OTO - NOTNLM OT - endothelial cell OT - erectile function OT - fibrosis OT - human tissue kallikrein-1 OT - hyperhomocysteinemia OT - oxidative stress COIS- None EDAT- 2019/01/09 06:00 MHDA- 2020/08/06 06:00 PMCR- 2019/01/01 CRDT- 2019/01/09 06:00 PHST- 2019/01/09 06:00 [pubmed] PHST- 2020/08/06 06:00 [medline] PHST- 2019/01/09 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - 249478 [pii] AID - AJA-21-508 [pii] AID - 10.4103/aja.aja_111_18 [doi] PST - ppublish SO - Asian J Androl. 2019 Sep-Oct;21(5):508-515. doi: 10.4103/aja.aja_111_18.