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首页> 外文期刊>Cellular Physiology and Biochemistry >Thyroid Hormone Beta Receptor Mutation Causes Renal Dysfunction and Impairment of ClC-2 Chloride Channel Expression in Mouse Kidney
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Thyroid Hormone Beta Receptor Mutation Causes Renal Dysfunction and Impairment of ClC-2 Chloride Channel Expression in Mouse Kidney

机译：甲状腺激素β受体突变导致小鼠肾功能障碍和ClC-2氯离子通道表达受损。

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Background/Aims Mutations in the thyroid hormone receptor β (TR-β) gene result in resistance to thyroid hormone (RTH). Mutation Δ337T in the TR-β gene has been shown to have the characteristics of RTH syndrome in mice. The aim of this work was to study the possible involvement of TR-β receptor in thyroid modulation of ClC-2 in mouse kidney. Methods Expression of mouse (Δ337T and normal C57BL/6) renal RNA and protein expression were studied by reverse transcriptase-polymerase chain reaction and Western blot, respectively, in mice with hyper- or hypothyroidism. Renal function was studied by analysis of urinary electrolyte excretion. Studies of the ClC-2 promoter region were performed in immortalized renal proximal tubule (IRPT) cells. Results In RTH syndrome mice (Δ337T), renal dysfunction was found to be associated with changes in the fractional excretion of sodium (FEsubNa/sub) and chloride (FEsubCl/sub). ClC-2 chloride channel mRNA and protein expression were found to be decreased by 40% in heterozygous and homozygous mutant mouse kidneys and high levels of plasma thyroid hormone were detected in both groups. Hypothyroidism induced by methimazole decreased the renal expression of ClC-2 in normal mice but not in Δ337T mutant mice. In iin vitro/i studies performed on IRPT cells subjected to thyroid hormone treatment, the promoter region of the ClC-2 chloride channel was stimulated in a dose-dependent manner. Conclusions This work emphasizes the importance of thyroid hormone in electrolyte handling along the nephron and suggests its participation in renal ClC-2 gene transcription via the TR-β receptor pathway.
机译：背景/目的甲状腺激素受体β（TR-β）基因的突变导致对甲状腺激素（RTH）的耐药。研究表明，TR-β基因中的Δ337T突变具有RTH综合征的特征。这项工作的目的是研究TR-β受体可能参与小鼠肾脏ClC-2的甲状腺调节。方法采用逆转录-聚合酶链反应和Western blot方法分别对甲状腺功能亢进或甲状腺功能低下的小鼠肾脏（Δ337T和正常C57BL / 6）肾RNA和蛋白表达进行研究。通过分析尿电解质排泄来研究肾功能。在永生化的肾近端小管（IRPT）细胞中进行了ClC-2启动子区域的研究。结果在RTH综合征小鼠（Δ337T）中，发现肾功能不全与钠（FE Na ）和氯化物（FE Cl ）的分数排泄变化有关。发现杂合子和纯合子突变小鼠肾脏中ClC-2氯化物通道的mRNA和蛋白表达降低了40％，并且在两组中均检测到高水平的血浆甲状腺激素。甲巯咪唑引起的甲状腺功能减退症降低了正常小鼠中ClC-2的肾脏表达，但没有降低Δ337T突变小鼠的肾脏表达。在对经过甲状腺激素处理的IRPT细胞进行的体外研究中，ClC-2氯化物通道的启动子区域以剂量依赖性方式被刺激。结论这项工作强调了甲状腺激素在沿肾单位进行电解质处理中的重要性，并暗示其通过TR-β受体途径参与了肾脏ClC-2基因的转录。

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