JAK2 deficiency improves erectile function in diabetic mice through attenuation of oxidative stress, apoptosis, and fibrosis.
JAK2 deficiency improves erectile function in diabetic mice through attenuation of oxidative stress, apoptosis, and fibrosis.
复制标题
JAK2缺陷通过减轻氧化应激、细胞凋亡和纤维化改善糖尿病小鼠的勃起功能。
作者：
Li H;Xu W;Liu X;Wang T;Wang S;Liu J;Jiang H
Janus 激酶 2 (JAK2) 在糖尿病 (DM) 情况下被激活，可能会增强许多组织的氧化应激、细胞凋亡和纤维化。 JAK2激活是否与糖尿病勃起功能障碍(ED)的发生有关尚不清楚。我们进行这项研究是为了调查 JAK2 缺陷对糖尿病 ED 的影响。使用条件JAK2基因敲除小鼠（Cre +/+-JAK2fl/fl ），其中他莫昔芬可以诱导JAK2基因敲除。小鼠分为四组：对照组、JAK2 敲除组 (JAK2−/−)、DM 组和带有 JAK2−/− 的 DM 组。通过腹腔注射链脲佐菌素诱导DM。两个月后，在 Cre+/+-JAK2fl/fl 小鼠中用他莫昔芬诱导 JAK2 基因敲除。再过两个月后，通过电刺激海绵体神经来测量勃起功能，并采集阴茎组织。测量海绵体内最大海绵体内压（MIP）与平均动脉压（MAP）的比值、JAK2的表达和磷酸化、氧化应激水平、NO/环磷酸鸟苷（cGMP）途径、细胞凋亡、纤维化以及海绵体中转化生长因子β1（TGF-β1）/Smad/IV胶原蛋白途径。用他莫昔芬诱导后，JAK2 表达显着降低。 JAK2在糖尿病小鼠的阴茎组织中被激活，JAK2缺乏可以改善DM引起的勃起功能受损。然而，在没有 DM 的小鼠中，JAK2 缺乏对勃起功能没有明显影响。糖尿病小鼠的氧化应激、细胞凋亡、纤维化和 TGF-β1/Smad/IV 胶原蛋白通路水平均升高，而 JAK2 缺乏则减轻了糖尿病小鼠的这些变化。此外，JAK2 缺陷改善了糖尿病小鼠中下调的 NO/cGMP 通路的表达。在非糖尿病小鼠中，JAK2基因敲除后上述参数未发现明显变化。我们的研究表明，JAK2 缺陷可以改善糖尿病小鼠的勃起功能，这可能是通过减少海绵体氧化应激、细胞凋亡和纤维化来介导的。
Janus kinase 2 (JAK2) is activated in diabetic mellitus (DM) conditions and may enhance oxidative stress, apoptosis and fibrosis in many tissues. Whether JAK2 activation is involved in the occurrence of diabetic erectile dysfunction (ED) is unknown. We performed this study to investigate the effect of JAK2 deficiency on diabetic ED. Conditional JAK2 gene knockout mice (Cre +/+‐JAK2fl/fl ) were used, in which JAK2 gene knockout could be induced by tamoxifen. Mice fell into four groups: control, JAK2 knockout (JAK2−/−), DM, and DM with JAK2−/−. DM was induced by intraperitoneal injection of streptozotocin. Two months later, JAK2 gene knockout was induced with tamoxifen in Cre+/+‐JAK2fl/fl mice. After another 2 months, erectile function was measured by electrical stimulation of the cavernous nerve, and penile tissues were harvested. Ratio of maximal intracavernosal pressure (MIP) to mean arterial blood pressure (MAP), expression and phosphorylation of JAK2, oxidative stress level, NO/Cyclic Guanosine Monophosphate (cGMP) pathway, apoptosis, fibrosis, and transforming growth factor beta 1 (TGF‐β1)/Smad/Collagen IV pathway in corpus cavernosum, were measured. JAK2 expression was remarkably decreased after induction with tamoxifen. JAK2 was activated in penile tissues of diabetic mice, and JAK2 deficiency could improve the impaired erectile function caused by DM. However, in mice without DM, JAK2 deficiency had no apparent influence on erectile function. Levels of oxidative stress, apoptosis, fibrosis, and TGF‐β1/Smad/Collagen IV pathway were all elevated by DM, whereas JAK2 deficiency lessened these alterations in diabetic mice. Moreover, JAK2 deficiency improved the expression of the down‐regulated NO/cGMP pathway in diabetic mice. In non‐diabetic mice, no apparent changes were found in aforementioned parameters after JAK2 gene knockout. Our study showed that JAK2 deficiency could improve erectile function in diabetic mice, which might be mediated by reduction in oxidative stress, apoptosis, and fibrosis in corpus cavernosum.
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影响因子：
4
作者：
Francis, Sharron H.;Corbin, Jackie D.
通讯作者：
Corbin, Jackie D.
影响因子：
10.8
作者：
Kirabo, Annet;Kearns, Patrick N.;Sayeski, Peter P.
通讯作者：
Sayeski, Peter P.
影响因子：
3.5
作者：
Gonzalez-Cadavid, Nestor F.
通讯作者：
Gonzalez-Cadavid, Nestor F.
影响因子：
3.7
作者：
Li M;Li H;Ruan Y;Wang T;Liu J
通讯作者：
Liu J
DOI：
10.1152/ajprenal.00251.2009
发表时间：
2009-11-01
影响因子：
4.2
作者：
Ponnusamy, Murugavel;Pang, Maoyin;Zhuang, Shougang
通讯作者：
Zhuang, Shougang