The sodium/glucose cotransporters as potential therapeutic targets for CF lung diseases revealed by human lung organoid swelling assay
dc.contributor.author | Hirai, H | |
dc.contributor.author | Liang, X | |
dc.contributor.author | Sun, Y | |
dc.contributor.author | Zhang, Y | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Chen, YE | |
dc.contributor.author | Mou, H | |
dc.contributor.author | Zhao, Y | |
dc.contributor.author | Xu, J | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-10-05T14:30:56Z | |
dc.date.available | 2022-10-05T14:30:56Z | |
dc.date.issued | 2022-03-10 | |
dc.identifier.issn | 2329-0501 | |
dc.identifier.issn | 2329-0501 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/34977268 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/174881 | en |
dc.description.abstract | Cystic fibrosis (CF) is a lethal autosomal-recessive inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the present work, we derived human proximal lung organoids (HLOs) from patient-derived pluripotent stem cells (PSCs) carrying disease-causing CFTR mutations. We evaluated the forskolin (Fsk)-stimulated swellings of these HLOs in the presence of CFTR modulators (VX-770 and/or VX-809) and demonstrated that HLOs respond to CFTR modulators in a mutation-dependent manner. Using this assay, we examined the effects of the sodium-dependent glucose cotransporter 1/2 (SGLT1/2) inhibitor drugs phlorizin and sotagliflozin on the basis of our findings that SGLT1 expression is upregulated in CF HLOs and airway epithelial cells compared with their wild-type counterparts. Unexpectedly, both drugs promoted dF/dF HLO swelling. These results reveal SGLTs, especially SGLT1, as potential therapeutic targets for treating CF lung diseases and demonstrate the use of PSC-derived HLOs as a preclinical tool in CF drug development. | |
dc.format.medium | Electronic-eCollection | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | CFTR | |
dc.subject | SGLT | |
dc.subject | cystic fibrosis | |
dc.subject | drug discovery | |
dc.subject | human induced pluripotent stem cells (hiPSCs) | |
dc.subject | inhibitor | |
dc.subject | lung organoids | |
dc.subject | sodium/glucose cotransporters | |
dc.subject | sotagliflozin | |
dc.title | The sodium/glucose cotransporters as potential therapeutic targets for CF lung diseases revealed by human lung organoid swelling assay | |
dc.type | Article | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/174881/2/The sodiumglucose cotransporters as potential therapeutic targets for CF lung diseases revealed by human lung organoid swell.pdf | |
dc.identifier.doi | 10.1016/j.omtm.2021.11.008 | |
dc.identifier.doi | https://dx.doi.org/10.7302/6510 | |
dc.identifier.source | Molecular Therapy - Methods and Clinical Development | |
dc.description.version | Published version | |
dc.date.updated | 2022-10-05T14:30:53Z | |
dc.identifier.orcid | 0000-0001-7302-7587 | |
dc.identifier.orcid | 0000-0001-9169-0390 | |
dc.identifier.orcid | 0000-0001-9862-7685 | |
dc.identifier.orcid | 0000-0001-5161-4705 | |
dc.identifier.orcid | 0000-0003-2357-7825 | |
dc.identifier.orcid | 0000-0002-0041-0339 | |
dc.identifier.volume | 24 | |
dc.identifier.startpage | 11 | |
dc.identifier.endpage | 19 | |
dc.identifier.name-orcid | Hirai, H; 0000-0001-7302-7587 | |
dc.identifier.name-orcid | Liang, X; 0000-0001-9169-0390 | |
dc.identifier.name-orcid | Sun, Y; 0000-0001-9862-7685 | |
dc.identifier.name-orcid | Zhang, Y | |
dc.identifier.name-orcid | Zhang, J; 0000-0001-5161-4705 | |
dc.identifier.name-orcid | Chen, YE; 0000-0003-2357-7825 | |
dc.identifier.name-orcid | Mou, H | |
dc.identifier.name-orcid | Zhao, Y; 0000-0002-0041-0339 | |
dc.identifier.name-orcid | Xu, J | |
dc.working.doi | 10.7302/6510 | en |
dc.owningcollname | Internal Medicine, Department of |
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