PDF(Pubmed)
Abstract：
Heat shock factors (HSFs) are the main transcriptional regulators of the evolutionarily conserved heat shock response. Beyond cell stress, several studies have demonstrated that HSFs also contribute to a vast variety of human pathologies, ranging from metabolic diseases to cancer and neurodegeneration. Despite their evident role in mitigating cellular perturbations, the functions of HSF1 and HSF2 in physiological proteostasis have remained inconclusive. Here, we analyzed a comprehensive selection of paraffin-embedded human tissue samples with immunohistochemistry. We demonstrate that both HSF1 and HSF2 display distinct expression and subcellular localization patterns in benign tissues. HSF1 localizes to the nucleus in all epithelial cell types, whereas nuclear expression of HSF2 was limited to only a few cell types, especially the spermatogonia and the urothelial umbrella cells. We observed a consistent and robust cytoplasmic expression of HSF2 across all studied smooth muscle and endothelial cells, including the smooth muscle cells surrounding the vasculature and the high endothelial venules in lymph nodes. Outstandingly, HSF2 localized specifically at cell-cell adhesion sites in a broad selection of tissue types, such as the cardiac muscle, liver, and epididymis. To the best of our knowledge, this is the first study to systematically describe the expression and localization patterns of HSF1 and HSF2 in benign human tissues. Thus, our work expands the biological landscape of these factors and creates the foundation for the identification of specific roles of HSF1 and HSF2 in normal physiological processes.
摘要：
热休克因子（HSF）是进化保守的热休克反应的主要转录调节因子。除了细胞压力，一些研究表明，HSF也有助于各种各样的人类病理，从代谢性疾病到癌症和神经变性。尽管它们在减轻细胞扰动方面具有明显的作用，HSF1和HSF2在生理蛋白稳定中的功能尚未确定。这里,我们用免疫组织化学分析了石蜡包埋的人组织样本的综合选择。我们证明了HSF1和HSF2在良性组织中显示出不同的表达和亚细胞定位模式。HSF1定位于所有上皮细胞类型的细胞核，而HSF2的核表达仅限于少数细胞类型，特别是精原细胞和尿路上皮伞状细胞。我们在所有研究的平滑肌细胞和内皮细胞中观察到HSF2的一致和稳健的细胞质表达，包括血管周围的平滑肌细胞和淋巴结中的高内皮小静脉。出色的,HSF2在广泛的组织类型中特异性定位在细胞-细胞粘附位点，比如心肌，肝脏,还有附睾.据我们所知,这是首次系统地描述HSF1和HSF2在人体良性组织中的表达和定位模式的研究。因此，我们的工作扩展了这些因素的生物景观，并为识别HSF1和HSF2在正常生理过程中的特定作用奠定了基础。
