Dataset Information

Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients.

ABSTRACT: Saliva secretion requires effective translocation of aquaporin 5 (AQP5) water channel to the salivary glands (SGs) acinar apical membrane. Patients with Sjögren's syndrome (SS) display abnormal AQP5 localization within acinar cells from SGs that correlate with sicca manifestation and glands hypofunction. Several proteins such as Prolactin-inducible protein (PIP) may regulate AQP5 trafficking as observed in lacrimal glands from mice. However, the role of the AQP5-PIP complex remains poorly understood. In the present study, we show that PIP interacts with AQP5 in vitro and in mice as well as in human SGs and that PIP misexpression correlates with an altered AQP5 distribution at the acinar apical membrane in PIP knockout mice and SS hMSG. Furthermore, our data show that the protein-protein interaction involves the AQP5 C-terminus and the N-terminal of PIP (one molecule of PIP per AQP5 tetramer). In conclusion, our findings highlight for the first time the role of PIP as a protein controlling AQP5 localization in human salivary glands but extend beyond due to the PIP-AQP5 interaction described in lung and breast cancers.

SUBMITTER: Chivasso C

PROVIDER: S-EPMC8391295 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients.

Chivasso Clara C Nesverova Veronika V Järvå Michael M Blanchard Anne A Rose Kristie L KL Öberg Fredrik Kryh FK Wang Zhen Z Martin Maud M Lhotellerie Florent F Zindy Egor E Junqueira Bruna B Leroy Karelle K Vanhollebeke Benoit B Delforge Valérie V Bolaky Nargis N Perret Jason J Soyfoo Muhammad Shahnawaz MS Moscato Stefania S Baldini Chiara C Chaumont François F Mattii Letizia L Schey Kevin L KL Myal Yvonne Y Törnroth-Horsefield Susanna S Delporte Christine C

Cells 20210817 8

Saliva secretion requires effective translocation of aquaporin 5 (AQP5) water channel to the salivary glands (SGs) acinar apical membrane. Patients with Sjögren's syndrome (SS) display abnormal AQP5 localization within acinar cells from SGs that correlate with sicca manifestation and glands hypofunction. Several proteins such as Prolactin-inducible protein (PIP) may regulate AQP5 trafficking as observed in lacrimal glands from mice. However, the role of the AQP5-PIP complex remains poorly unders ...[more]

PMID: 34440877

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Project description:RationalePSMA-directed therapy for metastatic prostate cancer is gaining adoption as a treatment option. However, accumulation of 177Lu/225Ac-PSMA in the salivary glands remains a problem, with risk of dose-limiting xerostomia and potentially severe effect on the quality of life. Gustatory stimulation is an approach that has commonly been used in radioactive iodine therapy to reduce accumulation in the salivary glands. However, based on theoretical differences in biodistribution, it was hypothesized that this could potentially lead to adverse increased toxicity for PSMA-ligand therapy. The primary objective of this work was to determine if gustatory stimulation by eating an assortment of sweet/fatty/acidic foods during the biodistribution phase of [18F]DCFPyl could result in a clinically relevant (> 30%) change in the uptake of the tracer in the salivary glands.Methods10 patients who already received a whole-body [18F]DCFPyl PET/CT scan for evaluation of prostate cancer, underwent a repeat (intervention) PET/CT scan within a month of the first (control) scan. During the intervention scan, patients chose from an assortment of sweet/fatty/acidic foods, which they then chewed and swallowed for a period of time starting 1 min before tracer administration to 10 min thereafter. Data from both scans were analyzed by placing VOIs on the major salivary glands and segmenting them using relative thresholds.ResultsA slight increase in PSMA uptake in the parotid glands was observed on the intervention scan when compared to the baseline scan (+ 7.1% SULmean and + 9.2% SULmax, p < 0.05). No significant difference in PSMA uptake in the submandibular glands was seen.ConclusionsEating only slightly increases uptake of [18F]DCFPyl in the parotid glands. We nonetheless recommend refraining from gustatory stimulation during the administration and early biodistribution phase of radionuclide therapy with PSMA-ligands to reduce the risk of avoidable additional toxicity.

Dataset Information

Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients.

Publications

Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients.

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