cellular prion protein expression as a novel marker of pulmonary fibrosis and clinical significance of cellular prion proein during pulmonary fibrosis

朊蛋白（PrPc）在正常和纤维化仓鼠肺中的细胞异构体表达。在未经治疗的肺中，Clara细胞阳性染色，其优先分布在小细支气管中，以球状颗粒为特征。反应产物在颗粒和细胞核外的细胞质中扩散。博莱霉素诱导的肺纤维化，在终末细支气管周围增厚的纤维组织中诱导细支气管增生。该事件的特征是导管结构的积累，主要由代表Clara细胞的PrPc阳性细胞排列。此外，在肺泡管上皮和再上皮的肺泡上皮中偶见PrPc阳性细胞。这些发现提示Clara细胞可能从终末细支气管增殖并迁移到腺泡。纤维组织中含有大量α -平滑肌肌动蛋白阳性的肌成纤维细胞。本研究表明，PrPc在正常和纤维化仓鼠肺的Clara细胞中表达，提示Clara细胞可能作为肺干细胞增殖并修复肺泡损伤后受损的上皮。作为临床医学研究，本研究旨在通过切除标本中PrPc的表达来评价接受放化疗患者的合理放疗面积和剂量。但在肺泡管上皮和再上皮的肺泡中未见PrPc阳性细胞；RT-PCR未检测到PrPc mRNA。这种后果可能是放化疗后约8周完全肺纤维化引起的。我们打算在放化疗后不久，即完全肺纤维化之前估计切除的标本。

Cellular isoform of prion protein (PrPc) expression in normal and fibrotic hamster lungs. In untreated lungs, Clara cells, which were preferentially distributed in small bronchioles and characterized by globule granules, were positively stained. Reactive products were diffused in the cytoplasm outside the granules and nuclei. In bleomycin-induced pulmonary fibrosis, bronchiolar proliferation was induced in the thickened fibrous tissue around terminal bronchioles. This event was characterized by accumulation of ductular structures which were predominantly lined by PrPc positive cells representative of Clara cells. Furthermore, PrPc positive cells were occasionally populated in the epithelium of alveolar ducts and reepithelialized alveoli. These findings suggest that Clara cells might undergo proliferation and migration into acini from terminal bronchioles. The fibrous tissue contained many alpha-smooth muscle actin positive myofibroblasts. The present study indicated that PrPc is expressed in Clara cells in normal and fibrotic hamster lungs and suggests that Clara cells may proliferate as pulmonary stem cells and repair the damaged epithelium after alveolar injuries.As clinical medical research this study aimed to evaluate the reasonable radiation area and dose for the patients who were treated with chemoradiation therapy using PrPc expression of resected specimens. But no PrPc positive cells were populated in the epithelium of alveolar ducts and reepithelialized alveoli immunohistochemically; furthermore PrPc mRNA was not detected by RT-PCR. This consequence may be caused by complete pulmonary fibrosis about 8 weeks after chemoradiation therapy. We intend to estimate the esected specimens soon after chemoradiation therapy, just before the complete pulmonary fibrosis.