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Enhanced glycolysis-mediated energy production in alveolar stem cells is required for alveolar regeneration. 2023

Zheng Wang, and Dongdong Wei, and Ennan Bin, and Jiao Li, and Kewu Jiang, and Tingting Lv, and Xiaoxu Mao, and Fengchao Wang, and Huaping Dai, and Nan Tang
National Institute of Biological Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China.

Impaired differentiation of alveolar stem cells has been identified in a variety of acute and chronic lung diseases. In this study, we investigate the mechanisms that modulate alveolar regeneration and understand how aging impacts this process. We have discovered that the process of alveolar type II (AT2) cells differentiating into AT1 cells is an energetically costly process. During alveolar regeneration, activated AMPK-PFKFB2 signaling upregulates glycolysis, which is essential to support the intracellular energy expenditure that is required for cytoskeletal remodeling during AT2 cell differentiation. AT2 cells in aged lungs exhibit reduced AMPK-PFKFB2 signaling and ATP production, resulting in impaired alveolar regeneration. Activating AMPK-PFKFB2 signaling in aged AT2 cells can rescue defective alveolar regeneration in aged mice. Thus, beyond demonstrating that cellular energy metabolism orchestrates with stem cell differentiation during alveolar regeneration, our study suggests that modulating AMPK-PFKFB2 signaling promotes alveolar repair in aged lungs.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D006019 Glycolysis A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH. Embden-Meyerhof Pathway,Embden-Meyerhof-Parnas Pathway,Embden Meyerhof Parnas Pathway,Embden Meyerhof Pathway,Embden-Meyerhof Pathways,Pathway, Embden-Meyerhof,Pathway, Embden-Meyerhof-Parnas,Pathways, Embden-Meyerhof
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055372 AMP-Activated Protein Kinases Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP. 5'-AMP-Activated Protein Kinase,AMP-Activated Kinase,AMP-Activated Protein Kinase,AMP-Activated Protein Kinase alpha Subunit,AMP-Activated Protein Kinase alpha Subunits,AMP-Activated Protein Kinase beta Subunit,AMP-Activated Protein Kinase beta Subunits,AMP-Activated Protein Kinase gamma Subunit,AMP-Activated Protein Kinase gamma Subunits,PRKAA,5' AMP Activated Protein Kinase,AMP Activated Kinase,AMP Activated Protein Kinase,AMP Activated Protein Kinase alpha Subunit,AMP Activated Protein Kinase alpha Subunits,AMP Activated Protein Kinase beta Subunit,AMP Activated Protein Kinase beta Subunits,AMP Activated Protein Kinase gamma Subunit,AMP Activated Protein Kinase gamma Subunits,AMP Activated Protein Kinases
D056809 Alveolar Epithelial Cells Epithelial cells that line the PULMONARY ALVEOLI. Pneumocytes,Alveolar Cells,Pneumocyte,Type 1 Pneumocytes,Type 2 Pneumocytes,Type-I Pneumocytes,Type-II Pneumocytes,Alveolar Cell,Alveolar Epithelial Cell,Cell, Alveolar,Cell, Alveolar Epithelial,Cells, Alveolar,Cells, Alveolar Epithelial,Epithelial Cell, Alveolar,Epithelial Cells, Alveolar,Pneumocyte, Type 1,Pneumocyte, Type 2,Pneumocyte, Type-I,Pneumocyte, Type-II,Pneumocytes, Type 1,Pneumocytes, Type 2,Pneumocytes, Type-I,Pneumocytes, Type-II,Type 1 Pneumocyte,Type 2 Pneumocyte,Type I Pneumocytes,Type II Pneumocytes,Type-I Pneumocyte,Type-II Pneumocyte

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