研究动态
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胰腺导管器官样体肿胀依赖氯离子。

Pancreatic duct organoid swelling is chloride-dependent.

发表日期:2023 Aug 24
作者: Yunxia O'Malley, Keyan Zarei, Oriana G Calderon Vanegas, Pratibha Singh, T Idil Apak, Mitchell Coleman, Ian M Thornell, Aliye Uc
来源: DIABETES & METABOLISM

摘要:

囊性纤维化(CF)导致胰液和碳酸盐分泌物黏稠和酸性化,突显了CFTR在胰液和碳酸盐分泌中的作用。在肠道类器官中发展出的丙酮酸盐诱导肿胀(FIS)检测方法可以测量剩余的CFTR功能。目前尚不清楚FIS是否反映了胰腺所分泌的近等渗NaHCO3水平的碳酸盐分泌。为了探究这个问题,我们从CF和非CF猪身上培养了胰管类器官样细胞团。采用上皮标记物、离子转运体以及没有腺泡、胰岛细胞标记物的确认了上皮和导管的起源。CF类器官样细胞团很小,没有可识别的腔隙;只有非CF类器官样细胞团中表达了CFTR。利用FIS,只有在氯离子作用下器官样细胞团的大小才会增加,而不是在碳酸盐作用下。本研究报道了首次从CF猪体中分离到的胰管类器官样细胞团,以及氯离子而不是碳酸盐推动胰腺类器官样细胞团肿胀的证据。这些类器官样细胞团对于检测导致CF胰腺疾病的CFTR突变体的氯离子渗透性将会很有用。版权所有 © 2023. Elsevier B.V.出版
Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO3 levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.Copyright © 2023. Published by Elsevier B.V.