Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection.
Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection.
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DOI：
10.1371/journal.pone.0136381
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Miyagawa-Hayashino A
中科院分区：
文献类型：
--
作者：
Ozeki M;Salah A;Aini W;Tamaki K;Haga H;Miyagawa-Hayashino A
STK17A（一种丝氨酸/苏氨酸激酶）在肝脏中的生物学意义尚不清楚。我们分析了 HepG2 细胞和人肝组织中的 STK17A 表达。因此，我们研究了 STK17A 是否有助于识别肝移植后慢性排斥反应 (CR) 演变过程中的早期变化。采用RT-PCR和免疫荧光分析HepG2细胞中STK17A的表达。使用来自 CR 和健康供体的人类肝脏样本进行抗体微阵列分析。免疫组织化学用于验证 STK17A 在连续活检中对后续 CR 发展的临床效用。在 HepG2 细胞中发现了 STK17A 的一种新的短亚型。 STK17A 定位于 HepG2 细胞和人类肝脏的细胞核和胆小管中。 STK17A 的微阵列显示其通过 CR 减少同种异体肝移植失败。在CR的演变过程中，胆小管STK17A的染色模式逐渐从弥漫性线性变为局灶性间歇性。在明确诊断CR之前观察局灶性间歇性染色模式。总之，本研究首次发现 STK17A 在正常胆小管中的定位。自排斥过程早期以来，STK17A 的异常表达和定位与同种异体肝移植物的 CR 相关。
The biological significance of STK17A, a serine/threonine kinase, in the liver is not known. We analyzed STK17A expression in HepG2 cells and human liver tissue. Accordingly, we investigated whether STK17A could help in identifying earlier changes during the evolution of chronic rejection (CR) after liver transplantation. RT-PCR and immunofluorescence were used to analyze STK17A expression in HepG2 cells. Antibody microarray was performed using human liver samples from CR and healthy donors. Immunohistochemistry was used to verify the clinical utility of STK17A on sequential biopsies for the subsequent development of CR. A novel short isoform of STK17A was found in HepG2 cells. STK17A was localized in the nuclei and bile canaliculi in HepG2 cells and human livers. Microarray of STK17A revealed its decrease in failed liver allografts by CR. During the evolution of CR, the staining pattern of bile canalicular STK17A gradually changed from diffuse linear to focal intermittent. The focal intermittent staining pattern was observed before the definite diagnosis of CR. In conclusion, the present study was the first to find localization of STK17A in normal bile canaliculi. Abnormal expression and localization of STK17A were associated with CR of liver allografts since the early stage of the rejection process.