ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases
<i>ATP12A</i> encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/10/1455 |
| _version_ | 1827721551104966656 |
|---|---|
| author | Michał Dębczyński Giulia Gorrieri Damian Mojsak Floriana Guida Federico Zara Paolo Scudieri |
| author_facet | Michał Dębczyński Giulia Gorrieri Damian Mojsak Floriana Guida Federico Zara Paolo Scudieri |
| author_sort | Michał Dębczyński |
| collection | DOAJ |
| description | <i>ATP12A</i> encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating the composition and properties of the fluid and mucus lining the respiratory epithelia, which are essential to maintain the airway host defense and the respiratory health. Increased expression and activity of ATP12A in combination with the loss of other balancing activities, such as the bicarbonate secretion mediated by CFTR, leads to excessive acidification of the airway surface liquid and mucus dysfunction, processes that play relevant roles in the pathogenesis of cystic fibrosis and other chronic inflammatory respiratory disorders. In this review, we summarize the findings dealing with ATP12A expression, function, and modulation in the airways, which led to the consideration of ATP12A as a potential therapeutic target for the treatment of cystic fibrosis and other airway diseases; we also highlight the current advances and gaps regarding the development of therapeutic strategies aimed at ATP12A inhibition. |
| first_indexed | 2024-03-10T21:24:57Z |
| format | Article |
| id | doaj.art-e4fcc17ca85043fe808d9e56609ff549 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T21:24:57Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e4fcc17ca85043fe808d9e56609ff5492023-11-19T15:49:29ZengMDPI AGBiomolecules2218-273X2023-09-011310145510.3390/biom13101455ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory DiseasesMichał Dębczyński0Giulia Gorrieri1Damian Mojsak2Floriana Guida3Federico Zara4Paolo Scudieri52nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, PolandDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, Italy2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, PolandDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, 16132 Genoa, Italy<i>ATP12A</i> encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating the composition and properties of the fluid and mucus lining the respiratory epithelia, which are essential to maintain the airway host defense and the respiratory health. Increased expression and activity of ATP12A in combination with the loss of other balancing activities, such as the bicarbonate secretion mediated by CFTR, leads to excessive acidification of the airway surface liquid and mucus dysfunction, processes that play relevant roles in the pathogenesis of cystic fibrosis and other chronic inflammatory respiratory disorders. In this review, we summarize the findings dealing with ATP12A expression, function, and modulation in the airways, which led to the consideration of ATP12A as a potential therapeutic target for the treatment of cystic fibrosis and other airway diseases; we also highlight the current advances and gaps regarding the development of therapeutic strategies aimed at ATP12A inhibition.https://www.mdpi.com/2218-273X/13/10/1455ATP12Amodifier genesairway acidificationcystic fibrosisASLproton transport |
| spellingShingle | Michał Dębczyński Giulia Gorrieri Damian Mojsak Floriana Guida Federico Zara Paolo Scudieri ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases Biomolecules ATP12A modifier genes airway acidification cystic fibrosis ASL proton transport |
| title | ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases |
| title_full | ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases |
| title_fullStr | ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases |
| title_full_unstemmed | ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases |
| title_short | ATP12A Proton Pump as an Emerging Therapeutic Target in Cystic Fibrosis and Other Respiratory Diseases |
| title_sort | atp12a proton pump as an emerging therapeutic target in cystic fibrosis and other respiratory diseases |
| topic | ATP12A modifier genes airway acidification cystic fibrosis ASL proton transport |
| url | https://www.mdpi.com/2218-273X/13/10/1455 |
| work_keys_str_mv | AT michałdebczynski atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases AT giuliagorrieri atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases AT damianmojsak atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases AT florianaguida atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases AT federicozara atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases AT paoloscudieri atp12aprotonpumpasanemergingtherapeutictargetincysticfibrosisandotherrespiratorydiseases |