Article ; Online: Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.
The Journal of clinical investigation
2023 Volume 133, Issue 24
Abstract: Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of ...
| Abstract | Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema. |
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| MeSH term(s) | Mice ; Humans ; Animals ; Lung/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Stem Cells/metabolism ; Wnt Signaling Pathway ; Aging/genetics | |||||
| Chemical Substances | TOR Serine-Threonine Kinases (EC 2.7.11.1) | |||||
| Language | English | |||||
| Publishing date | 2023-12-15 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 3067-3 | |||||
| ISSN | 1558-8238 ; 0021-9738 | |||||
| ISSN (online) | 1558-8238 | |||||
| ISSN | 0021-9738 | |||||
| DOI | 10.1172/JCI171430 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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