NGAL knockdown reduced cigarette-smoke-extract-induced senescence and MMP2/MMP9 expression in alveolar macrophage experiments.
Evidence
This preclinical human-tissue and cell-model study measured NGAL in COPD lung alveolar macrophages and tested NGAL siRNA in CSE-treated MH-S cells with senescence, proliferation, MMP, and PI3K/Akt assays.
Caveat
The mechanistic results mainly come from an in vitro CSE-induced MH-S cell model, so they do not establish that NGAL knockdown improves emphysema or COPD outcomes in humans.
Simplified
BACKGROUND: The accumulation of senescent cells has been identified as a key factor in the progression of emphysema. This study aimed to explore the role of neutrophil gelatinase-associated lipocalin (NGAL), a known mediator of COPD, in CSE-induced senescent alveolar macrophages.
METHODS: NGAL and markers expression were quantified in the lungs of COPD patients. Meanwhile, double-immunofluorescence staining was used to detect NGAL levels in alveolar macrophages of COPD lung tissues. Using a cigarette smoke exposure (CSE)-induced cellular senescence model in MH-S cells. Effects of CSE on NGAL secretion in MH-S cells was assessed by ELISA. Western blotting analysis and SA-β-galactosidase staining were employed to measure cellular senescence markers. NGAL siRNA was used to knockdown NGAL expression. In addition, CCK8 was used to evaluate cell viability and proliferation of MH-S cells. The activation status of the PI3K/Akt pathway was determined by Western blotting.
RESULTS: NGAL was elevated in alveolar macrophages from COPD patients compared with healthy controls. In vitro, exposure to CSE induced senescence in MH-S cells and concurrently increased NGAL secretion. Notably, NGAL knockdown attenuated CSE-induced senescence in MH-S cells via the PI3K/Akt pathway. Furthermore, NGAL downregulation significantly reversed CSE-suppressed MH-S cells proliferation and reduced MMP2 and MMP9 expression in senescent MH-S cells.
CONCLUSIONS: These findings indicate that CSE upregulates NGAL in alveolar macrophages, thereby driving cellular senescence and MMP production through PI3K/Akt pathway.
Key numbers
9 of 4
Increased Expression
Subjects with elevated in alveolar macrophages compared to healthy controls.
-induced
MMP2 and MMP9 Reduction
MMP2 and MMP9 expression levels in senescent post knockdown.
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