Effect of visfatin on K(ATP) channel upregulation in colonic smooth muscle cells in diabetic colon dysmotility.
Effect of visfatin on K(ATP) channel upregulation in colonic smooth muscle cells in diabetic colon dysmotility.
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内脂素对糖尿病结肠运动障碍结肠平滑肌细胞 KATP 通道上调的影响
DOI：
10.18632/aging.203871
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发表时间：
2022-02-03
期刊：
影响因子：
--
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Yu T;Zhang L;Wang Y;Shen X;Lin L;Tang Y
糖尿病相关胃肠运动障碍的机制尚不清楚。本研究旨在探讨促炎脂肪因子visfatin （VF）在糖尿病大鼠结肠平滑肌收缩功能障碍中的作用及其机制。将20只Sprague-Dawley大鼠随机分为对照组和2型糖尿病组。测定血清和结肠肌肉组织中VF水平，测定头射时间和结肠平滑肌条收缩力，分析结肠肌肉组织中atp敏感钾（KATP）通道的表达。在体外，我们测试了VF对结肠平滑肌细胞（CSMCs）细胞内活性氧（ROS）水平、NF-κB核转录、KATP通道表达、细胞内Ca2+浓度和肌球蛋白轻链（MLC）磷酸化的影响。同时检测活性氧抑制剂NAC和NF-κB抑制剂BAY 11-7082对KATP表达的影响。糖尿病大鼠血清和结肠肌肉组织中VF水平升高，结肠远端射血反应时间延迟，结肠平滑肌条收缩力减弱，结肠肌肉组织中KATP通道表达增加。VF明显抑制正常大鼠结肠平滑肌条的收缩力。在培养的CSMCs中，VF引起ROS超载，增加NF-κB核转录活性，增加Kir6.1的表达，最终降低细胞内Ca2+水平和MLC磷酸化。NAC和BAY 11-7082抑制vf诱导的Kir6.1上调。综上所述，VF可能通过ROS/NF-κB通路上调KATP通道Kir6.1亚基的表达，干扰Ca2+信号通路，从而引起CSMCs的收缩功能障碍。
The mechanisms of diabetes-related gastrointestinal dysmotility remains unclear. This study aimed to investigate the effect and mechanisms of proinflammatory adipokine visfatin (VF) in the contractile dysfunction of diabetic rat colonic smooth muscle. Twenty Sprague-Dawley rats were randomly divided into control and type 2 diabetes mellitus groups. VF levels in the serum and colonic muscle tissues were tested, the time of the bead ejection and contractility of colonic smooth muscle strips were measured, and the expression of ATP-sensitive potassium (KATP) channels in the colonic muscle tissues was analyzed. In vitro, we tested VF’s effects on intracellular reactive oxygen species (ROS) levels, NF-κB’s nuclear transcription, KATP channel expression, intracellular Ca2+ concentrations, and myosin light chain (MLC) phosphorylation in colonic smooth muscle cells (CSMCs). The effects of NAC (ROS inhibitor) and BAY 11-7082 (NF-κB inhibitor) on KATP expression were also tested. Diabetic rats showed elevated VF levels in serum and colonic muscle tissues, a delayed distal colon ejection response time, weakened contractility of colonic smooth muscle strips, and increased KATP channel expression in colonic muscle tissues. VF significantly inhibited the contractility of colonic smooth muscle strips from normal rats. In cultured CSMCs, VF caused ROS overload, increased NF-κB nuclear transcription activity and increased expression of Kir6.1, eventually reducing intracellular Ca2+ levels and MLC phosphorylation. NAC and BAY 11-7082 inhibited the VF–induced Kir6.1 upregulation. In conclusion, VF may cause contractile dysfunction of CSMCs by upregulating the expression of the Kir6.1 subunit of KATP channels via the ROS/NF-κB pathway and interfering with Ca2+ signaling.