Yang Erli, Ding Chandong, Zhu Xiaoxia, Zhang Jianming, Zhang Wen, Zhao Yufei, Zhang Jingjing, Lin Xianhe
Cardiovascular Department, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Cardiovascular Department for Gerontism, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Cardiovasc Diagn Ther. 2023 Jun 30;13(3):523-533. doi: 10.21037/cdt-23-105. Epub 2023 Jun 9.
To explore a new drug therapy for aldosterone-producing adenoma (APA), and investigate whether (secreted frizzled-related protein 2) can influence the development of adrenal APA by regulating the WNT/β-catenin pathway.
Tissue samples from APA patients were collected to detect the expression of and in APA. NCI-H295R cells were cultured with WNT/β-catenin pathway inhibitors to detect cell proliferation and aldosterone secretion. Then, the expression of was altered to determine the effect of expression on WNT/β-catenin pathway activity and aldosterone adenocarcinoma cells. Finally, a mouse APA model was established, and the mice were intravenously injected with WNT/β-catenin pathway inhibitors or transfected with the gene. The activity of the WNT/β-catenin pathway, blood pressure, aldosterone secretion, and cell growth in the mice were then observed.
was overexpressed in APA tissues, while was underexpressed. can negatively regulate expression and control the activity of the WNT/β-catenin pathway. Increased expression inhibited the activity of the WNT/β-catenin pathway, which suppressed aldosterone secretion and APA cell proliferation. The experiments also demonstrated that inhibition of WNT/β-catenin pathway activity in mice reduced the arterial pressure and aldosterone concentration. The increased expression of can inhibit the WNT/β-catenin pathway in mice, and can also reduce arterial pressure and APA tissue growth.
can inhibit the WNT/β-catenin signaling pathway by suppressing the expression of , thus controlling the concentration of aldosterone and hindering APA development. This study provides a novel therapeutic target for the treatment of APA and a new direction for future research.
探索一种治疗醛固酮分泌性腺瘤（APA）的新药物疗法，并研究分泌型卷曲相关蛋白2（sFRP2）是否可通过调节WNT/β-连环蛋白信号通路影响肾上腺APA的发展。
收集APA患者的组织样本，检测sFRP2和β-连环蛋白（β-catenin）在APA中的表达。用WNT/β-连环蛋白信号通路抑制剂培养NCI-H295R细胞，检测细胞增殖和醛固酮分泌。然后改变sFRP2的表达，以确定sFRP2表达对WNT/β-连环蛋白信号通路活性和醛固酮癌细胞的影响。最后，建立小鼠APA模型，给小鼠静脉注射WNT/β-连环蛋白信号通路抑制剂或转染sFRP2基因。随后观察小鼠体内WNT/β-连环蛋白信号通路的活性、血压、醛固酮分泌及细胞生长情况。
sFRP2在APA组织中过表达，而β-catenin表达下调。sFRP2可负向调节β-catenin的表达并控制WNT/β-连环蛋白信号通路的活性。sFRP2表达增加可抑制WNT/β-连环蛋白信号通路的活性，从而抑制醛固酮分泌和APA细胞增殖。动物实验还表明，抑制小鼠体内WNT/β-连环蛋白信号通路的活性可降低动脉血压和醛固酮浓度。sFRP2表达增加可抑制小鼠体内WNT/β-连环蛋白信号通路，还可降低动脉血压和APA组织生长。
sFRP2可通过抑制β-catenin的表达来抑制WNT/β-连环蛋白信号通路，从而控制醛固酮浓度并阻碍APA的发展。本研究为APA的治疗提供了一个新的治疗靶点及未来研究的新方向。
