Downregulation of Lysosome-Associated Membrane Protein-2A Contributes to the Pathogenesis of COPD

Yun Jeong Jeong, Kyoung Hee Lee, Jisu Woo, Ji Yeon Kim, Chang Hoon Lee, Chul Gyu Yoo

Research output: Contribution to journalArticlepeer-review


Background: Macroautophagy plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the role of chaperone-mediated autophagy (CMA) has not been investigated. We investigated if and how CMA is involved in the pathogenesis of COPD. Methods: We measured the level of lysosome-associated membrane protein-2A (LAMP-2A), which is a critical component of CMA that functions as a receptor for cytosolic substrate proteins, in total lung tissues and primary human bronchial epithelial cells (HBECs) from healthy never smokers, smokers, and COPD patients. We assessed the effects of LAMP-2A knock-down on cigarette smoke extract (CSE)-induced aging, cell cycle arrest, and apoptosis in BEAS-2B cells and the expression levels of apoptosis hallmarks in primary HBECs and lung tissue sections. Results: We found that the protein levels of LAMP-2A in lung homogenates and primary HBECs from smokers and COPD patients were lower than those from never smokers. In addition, its level in primary HBECs was negatively correlated with years of smoking. CSE caused degradation of LAMP-2A protein via the lysosomal pathway by activating macroautophagy. Knock-down of LAMP-2A markedly enhanced CSE-induced expression of senescence markers such as p16, p21, p27, and p53. G2/M cell cycle arrest, up-regulation of cyclin B1, and apoptosis in BEAS-2B cells. Apoptosis was increased in CSE-treated primary HBECs and in lung tissues from smokers and COPD patients. Conclusion: Cigarette smoke-induced down-regulation of LAMP-2A is involved in acceleration of aging and apoptosis of lung epithelial cells, which might at least partially contribute to COPD pathogenesis.

Original languageEnglish
Pages (from-to)289-303
Number of pages15
JournalInternational Journal of COPD
StatePublished - 2023
Externally publishedYes


  • COPD
  • LAMP-2A
  • aging
  • apoptosis
  • lung epithelial cells


Dive into the research topics of 'Downregulation of Lysosome-Associated Membrane Protein-2A Contributes to the Pathogenesis of COPD'. Together they form a unique fingerprint.

Cite this