Enhanced Peribiliary Gland Detachment in Aged Donor Grafts After Rat Liver Transplantation.

IF 2.2 Q3 TRANSPLANTATION
Transplantation Direct Pub Date : 2026-07-06 eCollection Date: 2026-08-01 DOI:10.1097/TXD.0000000000001981
Kaoru Katano, Shinichi Nakanuma, Takashi Sugio, Junichi Ogawa, Naoto Nishida, Hiroaki Horio, Ryohei Takei, Satoshi Takada, Mitsuyoshi Okazaki, Kaichiro Kato, Yasuhito Iwao, Isamu Makino, Kenichi Harada, Shintaro Yagi
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引用次数: 0

Abstract

Background: Older donor livers have higher rates of biliary complications after transplantation, but early mechanisms of bile duct injury remain incompletely understood. Peribiliary glands (PBGs) in the bile duct wall contain progenitor-like and secretory elements that may support epithelial maintenance and repair. We examined whether donor age is associated with early PBG injury and recovery and explored links with the basement-membrane component laminin.

Methods: Livers from young or aged rats were transplanted into young recipients. Extrahepatic bile ducts were evaluated before transplantation and at 24, 72, and 168 h after liver transplantation. PBG morphology and detachment, laminin γ1 expression, and markers related to progenitor-cell characteristics, mucus production, microvascular density, and apoptosis were assessed histologically and immunohistochemically.

Results: In aged donor grafts, PBGs showed progressive structural injury after transplantation, with marked cell detachment and loss of glandular architecture at 168 h. In contrast, PBGs in young donor grafts were largely preserved. Areas of PBG cell detachment in aged grafts were spatially associated with reduced laminin γ1 expression. Recovery of laminin γ1 expression over time was less evident in aged grafts and was accompanied by impaired progenitor-cell marker expression, reduced mucus production, persistently decreased microvascular density, and increased shedding of apoptotic PBG cells.

Conclusions: Aged donor grafts showed more pronounced early structural PBG injury after transplantation, together with persistent reduction of laminin γ1 expression.

老年大鼠肝移植后供体胆管周围腺脱离增强。
背景:年龄较大的供肝移植后胆道并发症发生率较高,但胆管损伤的早期机制仍不完全清楚。胆管壁的胆管周围腺(PBGs)含有祖细胞样和分泌因子,可能支持上皮的维持和修复。我们研究了供体年龄是否与早期PBG损伤和恢复有关,并探讨了与基底膜成分层粘连蛋白的联系。方法:将幼龄或老年大鼠肝脏移植到幼龄受者体内。肝外胆管在肝移植前和肝移植后24、72和168小时进行评估。用组织学和免疫组织化学方法评估PBG形态和脱离、层粘连蛋白γ - 1表达以及与祖细胞特征、粘液产生、微血管密度和凋亡相关的标志物。结果:老龄供体移植物移植后PBGs出现进行性结构损伤,在移植后168 h出现明显的细胞脱离和腺结构丧失。相比之下,年轻供体移植物中的pbg大部分保存完好。衰老移植物中PBG细胞脱离的区域与层粘连蛋白γ - 1表达的减少在空间上相关。随着时间的推移,层粘连蛋白γ - 1表达的恢复在衰老的移植物中不太明显,并伴有祖细胞标记物表达受损,粘液产生减少,微血管密度持续下降,凋亡的PBG细胞脱落增加。结论:老龄供移植物移植后早期结构PBG损伤更为明显,层粘连蛋白γ - 1表达持续降低。
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来源期刊
Transplantation Direct
Transplantation Direct TRANSPLANTATION-
CiteScore
3.40
自引率
4.30%
发文量
193
审稿时长
8 weeks
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