AI Article Synopsis
- - Alveolar type II (ATII) cells play a critical role in lung repair but their damage, often caused by cigarette smoke, contributes to the onset of emphysema, marked by destruction of alveolar walls.
- - Researchers examined ATII cells from non-smokers, smokers, and emphysema patients, focusing on the protein PICT1 and its role in disease progression, using both human cell analysis and a murine model.
- - Findings revealed decreased PICT1 levels in emphysema, linked to reduced DNA damage repair capabilities and mitochondrial dysfunction, suggesting that targeting PICT1 could lead to new treatments for the disease.
Article Abstract
Background: Alveolar type II (ATII) cells have a stem cell potential in the adult lung and repair the epithelium after injury induced by harmful factors. Their damage contributes to emphysema development, characterized by alveolar wall destruction. Cigarette smoke is the main risk factor for this disease development.
Methods: ATII cells were obtained from control non-smoker and smoker organ donors and emphysema patients. Isolated cells were used to study the role of PICT1 in this disease. Also, a cigarette smoke-induced murine model of emphysema was applied to define its function in disease progression further.
Results: Decreased PICT1 expression was observed in human and murine ATII cells in emphysema. PICT1 was immunoprecipitated, followed by mass spectrometry analysis. We identified MRE11, which is involved in DNA damage repair, as its novel interactor. PICT1 and MRE11 protein levels were decreased in ATII cells in this disease. Moreover, cells with PICT1 deletion were exposed to cigarette smoke extract. This treatment induced cellular and mitochondrial ROS, cell cycle arrest, nuclear and mitochondrial DNA damage, decreased mitochondrial respiration, and impaired DNA damage repair.
Conclusions: This study indicates that PICT1 dysfunction can negatively affect genome stability and mitochondrial activity in ATII cells, contributing to emphysema development. Targeting PICT1 can lead to novel therapeutic approaches for this disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583753 | PMC |
| http://dx.doi.org/10.1186/s12964-024-01896-0 | DOI Listing |
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