Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes.
Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes.
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DOI：
10.1016/j.bbrc.2016.12.109
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发表时间：
2017-01
影响因子：
3.1
通讯作者：
Kenzaburo Oda;Yuqian Luo;A. Yoshihara;Yuko Ishido;Kengo Sekihata;Kensei Usukura;M. Sue;N. Hiroi;T. Hirose;Koichi Suzuki
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文献类型：
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作者：
Kenzaburo Oda;Yuqian Luo;A. Yoshihara;Yuko Ishido;Kengo Sekihata;Kensei Usukura;M. Sue;N. Hiroi;T. Hirose;Koichi Suzuki
储存在甲状腺滤泡中的甲状腺球蛋白（Tg）通过抑制调节这些步骤的特异性转录因子的表达，对激素前体生物合成的每个步骤（包括Tg基因转录和碘摄取和有机化）发挥有效的负反馈作用。前激素在被重吸收之前储存在滤泡胶体中。甲状腺激素（TH）在其前体被溶酶体蛋白水解后，从甲状腺滤泡中释放出来。虽然卵泡Tg对前激素生物合成的每个步骤的抑制作用已被广泛表征，但卵泡Tg积累是否也影响激素重吸收、蛋白水解和分泌尚不清楚。在这项研究中，我们探讨了卵泡Tg是否可以调节溶酶体内肽酶组织蛋白酶的表达和功能。我们发现，在大鼠甲状腺细胞系FRTL-5滤泡Tg诱导组织蛋白酶H mRNA和蛋白质的表达，以及组织蛋白酶H酶的活性。双重免疫荧光染色显示，Tg内吞促进组织蛋白酶H转运到溶酶体中，在那里它与内化的Tg共定位。这些结果表明，组织蛋白酶H是一个积极的参与者在溶酶体介导的激素前体降解，并通过激活组织蛋白酶H相关的蛋白水解途径，卵泡Tg刺激动员激素前体。
Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of prehormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tg can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated prehormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways.