Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3K/AKT/eNOS Pathway
| العنوان: | Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3K/AKT/eNOS Pathway |
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| المؤلفون: | Jihong Liu, Kai Cui, Shaogang Wang, Kang Liu, Zhe Tang, Tao Wang, Yajun Ruan, Zhong Chen, Yang Luan |
| المصدر: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2020 (2020) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Blood Glucose, Male, Aging, medicine.medical_treatment, 030232 urology & nephrology, Apoptosis, medicine.disease_cause, Biochemistry, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Erectile Dysfunction, Enos, Fibrosis, Medicine, Cyclic GMP, biology, General Medicine, Fasting, 030220 oncology & carcinogenesis, Rats, Transgenic, Tissue Kallikreins, medicine.drug, Signal Transduction, Research Article, medicine.medical_specialty, Article Subject, Nitric Oxide Synthase Type III, Intraperitoneal injection, Myocytes, Smooth Muscle, Streptozocin, Diabetes Mellitus, Experimental, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Animals, Protein kinase B, PI3K/AKT/mTOR pathway, QH573-671, business.industry, Body Weight, Cell Biology, Streptozotocin, biology.organism_classification, medicine.disease, Electric Stimulation, Oxidative Stress, Endocrinology, Glucose, Calcium, business, Cytology, Proto-Oncogene Proteins c-akt, Oxidative stress, Penis |
| الوصف: | Objective. To investigate the protective effects and mechanisms of human tissue kallikrein 1 (hKLK1) on type 1 diabetes mellitus- (DM-) induced erectile dysfunction in rats. Materials and Methods. The homozygous transgenic rats (TGR) harboring the hKLK1 gene and age-matched wild-type Sprague Dawley rats (WTR) were involved, and intraperitoneal injection of streptozotocin was utilized to induce diabetes in rats. Forty-eight-week-old male rats were randomly divided into a WTR group, TGR group, diabetic WTR group (WTDM), diabetic TGR group (TGDM), and TGDM with HOE140 group (TGDMH), with eight rats in each group. Twelve weeks later, the erectile response of all rats was detected by cavernous nerve electric stimulation, and corpus cavernosums were harvested to evaluate the levels of cavernous oxidative stress (OS), apoptosis, fibrosis, and involved pathways. Moreover, cavernous smooth muscle cells (CSMC) and endothelial cells (EC) were primarily isolated to build a coculture system for a series of in vitro verification. Results. The hKLK1 gene only existed and was expressed in TGR. Compared to the WTR group, the WTDM group showed a lower erectile response, overactivated OS and apoptosis, inhibited PI3K/AKT/eNOS pathway, and aggravated cavernous fibrosis. However, hKLK1 in the TGDM group could improve these pathological changes induced by DM, while its protective effects could be weakened by HOE140 in the TGDMH group. In the coculture system, hKLK1 could induce CSMC relaxation through activating PI3K/eNOS/cGMP signaling and inhibiting calcium ion influx under physiological condition. It could also resist the increased reactive oxygen species, apoptosis level, and reduced cGMP level in CSMC under high-glucose condition. Conclusions. hKLK1 preserves erectile function of DM rats through its antitissue excessive OS, apoptosis, and fibrosis effects, as well as activation of the PI3K/AKT/eNOS/cGMP pathway in the penis. Moreover, hKLK1 promotes relaxation and prevents high glucose-induced injuries of CSMC mediated by EC-CSMC crosstalk. |
| وصف الملف: | text/xhtml |
| تدمد: | 1942-0994 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28d3312a7b8b45f46a60bee366bf8cdeTest https://pubmed.ncbi.nlm.nih.gov/32190176Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....28d3312a7b8b45f46a60bee366bf8cde |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19420994 |
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