Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
Biomed Res Int. 2021 Feb 23;2021:2471518. doi: 10.1155/2021/2471518. eCollection 2021.
Apoptotic events mediated by mitochondrial injury play an important role on the onset of Pemphigus vulgaris (PV). The thioredoxin-2 (Trx2)/apoptosis signal-regulating kinase 1 (ASK1) signaling pathway is considered a key cascade involved on the regulation of mitochondrial injury. Hence, we have investigated the regulatory mechanism of the Trx2/ASK1 signaling in PV-induced mitochondrial injury.
Serum and tissue samples were collected from clinical PV patients to detect the oxidative stress factors, cell apoptosis, and expression of members from Trx2/ASK1 signaling. HaCaT cells were cultured with the serum of PV patients and transfected with Trx2 overexpression or silencing vector. Changes in the levels of reactive oxygen species (ROS), mitochondrial membrane potential (△m), and apoptosis were further evaluated. A PV mouse model was established and administered with Trx2-overexpressing plasmid. The effect of ectopic Trx2 expression towards acantholysis in PV mice was observed.
A series of cellular and molecular effects, including (i) increased levels of oxidative stress products, (ii) destruction of epithelial cells in the skin tissues, (iii) induction of apoptosis in keratinocytes, (iv) reduction of Trx2 protein levels, and (v) enhanced phosphorylation of ASK1, were detected in PV patients. experiments confirmed that Trx2 can inhibit ASK1 phosphorylation, alleviate ROS release, decrease △m, and lower the apoptotic rate. Injection of Trx2-overexpressing vectors could also relieve acantholysis and blister formation in PV mice.
The Trx2/ASK1 signaling pathway regulates the incidence of PV mediated by mitochondrial injury.
线粒体损伤介导的凋亡事件在寻常型天疱疮（PV）的发病中起重要作用。硫氧还蛋白-2（Trx2）/凋亡信号调节激酶 1（ASK1）信号通路被认为是参与调节线粒体损伤的关键级联反应。因此，我们研究了 Trx2/ASK1 信号在 PV 诱导的线粒体损伤中的调节机制。
收集临床 PV 患者的血清和组织样本，检测氧化应激因子、细胞凋亡和 Trx2/ASK1 信号成员的表达。用 PV 患者的血清培养 HaCaT 细胞，并转染 Trx2 过表达或沉默载体。进一步评估活性氧（ROS）、线粒体膜电位（△m）和细胞凋亡的变化。建立 PV 小鼠模型并给予 Trx2 过表达质粒。观察外源性 Trx2 表达对 PV 小鼠棘层松解的影响。
一系列细胞和分子效应，包括（i）氧化应激产物水平升高，（ii）皮肤组织上皮细胞破坏，（iii）角质形成细胞凋亡诱导，（iv）Trx2 蛋白水平降低，和（v）ASK1 磷酸化增强，在 PV 患者中检测到。实验证实，Trx2 可抑制 ASK1 磷酸化，减轻 ROS 释放，降低△m，降低细胞凋亡率。注射 Trx2 过表达载体也可缓解 PV 小鼠的棘层松解和水疱形成。
Trx2/ASK1 信号通路调节线粒体损伤介导的 PV 发病。
