Academic Journal
Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661 + VX-770 treatment on disease severity
| العنوان: | Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661 + VX-770 treatment on disease severity |
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| المؤلفون: | Fűr Gabriella, Bálint Emese Réka, Orján Erik Márk, Balla Zsolt, Kormányos Eszter Sára, Czira Beáta, Szűcs Attila, Kovács Dénes Péter, Pallagi Petra, Maléth József, Venglovecz Viktória, Hegyi Péter, Kiss Lóránd, Rakonczay Zoltán Jr. |
| سنة النشر: | 2021 |
| المجموعة: | University of Szeged: SZTE Repository of Publications / SZTE Publicatio Repozitórium |
| مصطلحات موضوعية: | 03.01. Általános orvostudomány, 03.02. Klinikai orvostan |
| الوصف: | Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP). Here, we investigated the localization and expression of CFTR during cerulein-induced AP in mice and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. CFTR mRNA expression was significantly increased, and mislocalization of CFTR protein was observed in AP compared to the control group. Interestingly, pre-treatment of AP mice with VX-661 + VX-770 significantly reduced the extent of pancreatic tissue damage by 20-30%. In vitro administration of VX-661 + VX-770 significantly increased the fluid secretion of ducts derived from AP animals. Based on our results, the utilization of CFTR correctors and potentiators should be further investigated in AP.Cystic fibrosis transmembrane conductance regulator (CFTR) has essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. AP was induced in FVB/n mice by 6-10 hourly intraperitoneal injections of 50μg/kg cerulein. Some mice were pre-treated with 5-6 daily injections of 2mg/kg VX-661+VX-770. Control animals were administered physiological saline instead of cerulein and DMSO instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expressions were measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra-/interlobular ducts. Cerulein-induced AP severity was greatest between 12-24h. CFTR mRNA expression was significantly increased 24h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | http://publicatio.bibl.u-szeged.hu/22574/1/FurGJPhysiol2021accepted.pdf; Fűr Gabriella; Bálint Emese Réka; Orján Erik Márk; Balla Zsolt; Kormányos Eszter Sára; Czira Beáta; Szűcs Attila; Kovács Dénes Péter; Pallagi Petra; Maléth József; Venglovecz Viktória; Hegyi Péter; Kiss Lóránd; Rakonczay Zoltán Jr.: Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661 + VX-770 treatment on disease severity. JOURNAL OF PHYSIOLOGY-LONDON, 599 (22). pp. 4955-4971. ISSN 0022-3751 (2021) |
| DOI: | 10.1113/JP281765 |
| الاتاحة: | http://publicatio.bibl.u-szeged.hu/22574/ http://publicatio.bibl.u-szeged.hu/22574/1/FurGJPhysiol2021accepted.pdf https://doi.org/10.1113/JP281765 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BE4A3A89 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1113/JP281765 |
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