The Pervasive Effects of ER Stress on a Typical Endocrine Cell: Dedifferentiation, Mesenchymal Shift and Antioxidant Response in the Thyrocyte.
The Pervasive Effects of ER Stress on a Typical Endocrine Cell: Dedifferentiation, Mesenchymal Shift and Antioxidant Response in the Thyrocyte.
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DOI：
10.3389/fendo.2020.588685
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发表时间：
2020
影响因子：
5.2
通讯作者：
Di Jeso B
中科院分区：
文献类型：
--
作者：
Ulianich L;Mirra P;Garbi C;Calì G;Conza D;Treglia AS;Miraglia A;Punzi D;Miele C;Raciti GA;Beguinot F;Consiglio E;Di Jeso B
内质网应激和未折叠的蛋白质反应是在蛋白质负荷和蛋白质折叠不平衡后触发的。直到最近，人们还在考虑未折叠蛋白质反应的两种可能结果：生或死。我们试图通过使用典型的内分泌细胞，即甲状腺细胞，来证实第三种替代方案，即去分化、间充质移位和抗氧化反应的激活。甲状腺是一个独特的系统，既有内质网应激(一种单一蛋白质，甲状腺球蛋白代表甲状腺细胞在内质网合成的大部分蛋白质)，也有极化上皮(界定滤泡的单层甲状腺细胞)。内质网应激后，甲状腺细胞中甲状腺球蛋白的折叠被破坏。未折叠蛋白反应的mRNAs被诱导或剪接(X-box结合蛋白-1)。分化受到抑制：甲状腺特异基因和甲状腺转录因子的mRNA水平显著下调，至少部分是在转录方面。伴随着去分化反应的是抗氧化基因的mRNAs上调。此外，钙粘蛋白-1和甲状腺(和肾脏)特异的钙粘蛋白-16mRNAs表达下调，波形蛋白和SNAI1mRNAs表达上调。此外，还观察到皮质肌动蛋白的丢失和应力纤维的形成。综上所述，这些数据表明，甲状腺细胞中的内质网应激诱导去分化、上皮组织丧失、向间充质表型转变和抗氧化反应的激活，同时突显了在内质网应激后实现生存的新的广泛策略，以及作为硬币的另一面，可能是导致甲状腺激素形成障碍的功能下降/丧失的新的分子机制。
The endoplasmic reticulum stress and the unfolded protein response are triggered following an imbalance between protein load and protein folding. Until recently, two possible outcomes of the unfolded protein response have been considered: life or death. We sought to substantiate a third alternative, dedifferentiation, mesenchymal shift, and activation of the antioxidant response by using typical endocrine cells, i.e. thyroid cells. The thyroid is a unique system both of endoplasmic reticulum stress (a single protein, thyroglobulin represents the majority of proteins synthesized in the endoplasmic reticulum by the thyrocyte) and of polarized epithelium (the single layer of thyrocytes delimiting the follicle). Following endoplasmic reticulum stress, in thyroid cells the folding of thyroglobulin was disrupted. The mRNAs of unfolded protein response were induced or spliced (X-box binding protein-1). Differentiation was inhibited: mRNA levels of thyroid specific genes, and of thyroid transcription factors were dramatically downregulated, at least in part, transcriptionally. The dedifferentiating response was accompanied by an upregulation of mRNAs of antioxidant genes. Moreover, cadherin-1, and the thyroid (and kidney)-specific cadherin-16 mRNAs were downregulated, vimentin, and SNAI1 mRNAs were upregulated. In addition, loss of cortical actin and stress fibers formation were observed. Together, these data indicate that ER stress in thyroid cells induces dedifferentiation, loss of epithelial organization, shift towards a mesenchymal phenotype, and activation of the antioxidant response, highlighting, at the same time, a new and wide strategy to achieve survival following ER stress, and, as a sort of the other side of the coin, a possible new molecular mechanism of decline/loss of function leading to a deficit of thyroid hormones formation.
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DOI：
10.1016/j.bbamcr.2016.02.019
发表时间：
2016-06-01
影响因子：
5.1
作者：
Longo, Michele;Spinelli, Rosa;Di Jeso, Bruno
通讯作者：
Di Jeso, Bruno
影响因子：
4.1
作者：
Di Jeso, B;Ulianich, L;Arvan, P
通讯作者：
Arvan, P
影响因子：
5.3
作者：
Di Jeso, B;Park, YN;Arvan, P
通讯作者：
Arvan, P
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
4.8
作者：
Leonardi, A;Vito, P;Di Jeso, B
通讯作者：
Di Jeso, B