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

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

  • Cell Stem Cell. 2023 Aug 3;30(8):1028-1042.e7. doi: 10.1016/j.stem.2023.07.007.
Zheng Wang 1,  Dongdong Wei 2,  Ennan Bin 3,  Jiao Li 3,  Kewu Jiang 3,  Tingting Lv 4,  Xiaoxu Mao 5,  Fengchao Wang 5,  Huaping Dai 4,  Nan Tang 6
Affiliations

Affiliations

  • 1 National Institute of Biological Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China.
  • 2 National Institute of Biological Sciences, Beijing, China; Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Peking University, Beijing, China.
  • 3 National Institute of Biological Sciences, Beijing, China.
  • 4 Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
  • 5 National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
  • 6 National Institute of Biological Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China. Electronic address: tangnan@nibs.ac.cn.
PMID: 37541209 DOI: 10.1016/j.stem.2023.07.007
Abstract

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.

Keywords

aging; alveolar stem cells; energy metabolism; fibrosis resolution; lung regeneration; mechanical.

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