Evaluation Value of AKT/mTOR Signaling Pathway Expression in Peripheral Blood Mononuclear Cells in Patients with Chronic Obstructive Pulmonary Disease

Junjun ZHANG; Zhen LIANG; Yanfang PENG

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Junjun ZHANG, Zhen LIANG, Yanfang PENG. Evaluation Value of AKT/mTOR Signaling Pathway Expression in Peripheral Blood Mononuclear Cells in Patients with Chronic Obstructive Pulmonary Disease[J]. Journal of Kunming Medical University.

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Evaluation Value of AKT/mTOR Signaling Pathway Expression in Peripheral Blood Mononuclear Cells in Patients with Chronic Obstructive Pulmonary Disease

Department of Respiratory and Critical Care Medicine，Ordos Central Hospital，Ordos Inner Mongolia 017010，China

Received Date: 2025-07-07
Available Online: 2026-01-22

Abstract

Abstract

Objective To investigate the research value of AKT/mTOR signaling pathway expression in patients with chronic obstructive pulmonary disease （COPD） . Methods From January 2023 to June 2024, 20 healthy controls, 20 stable COPD （R-COPD） patients, and 20 acute exacerbation COPD （AE-COPD） patients were recruited from the Central Hospital of Ordos City. Peripheral venous blood samples were collected from all participants, with serum and peripheral blood mononuclear cells （PBMCs） isolated. Quantitative reverse transcription polymerase chain reaction （qRT-PCR） was employed to assess the expression levels of the AKT/mTOR signaling pathway in PBMCs. In vitro experiments involved human lung microvascular endothelial cells （HULEC-5a） and human bronchial epithelial cells （HBE）, which were categorized into control, cigarette smoke extract （CSE）, and AKT inhibitor MK-2206 groups. qRT-PCR, Western blot, and immunofluorescence techniques were utilized to evaluate the expression of the AKT/mTOR signaling pathway in each group. Through conditional medium co-culture experiments, HULEC-5a cell supernatant containing MK-2206 was introduced to the culture wells of lung fibroblasts or THP-1 cell line-derived macrophages, and cell migration ability was assessed using the Transwell method. Results No statistically significant differences were observed in gender, age, weight, height, and BMI among the three groups （P > 0.05）. In terms of lung function, the AE-COPD group exhibited lower FVC （72.08±10.78, % pred.）, FEV1 （47.21±11.32, % pred.）, and FEV1/FVC （58.67±11.68, %） compared to the R-COPD and healthy control groups （P < 0.05）. qRT-PCR analysis indicated higher AKT mRNA and mTOR mRNA expression in PBMCs of the AE-COPD group relative to the R-COPD and healthy control groups （F = 10.31, 13.23, P = 0.001）. In vitro experiments revealed that the CSE group had elevated AKT/mTOR mRNA and protein expression in HULEC-5a and HBE cells compared to the control group, while the MK-2206 group exhibited lower levels （P < 0.05）. Immunofluorescence quantification demonstrated increased AKT/mTOR fluorescence intensity in the CSE group and significantly reduced intensity in the MK-2206 group （F = 18.632, 17.853, P = 0.000）. Transwell experiments showed higher numbers of lung fibroblasts [（391.31±23.21） cells/field] and THP-1 macrophages [（411.25±32.65） cells/field] in the CSE group, with the MK-2206 group displaying reduced numbers compared to the CSE group （F = 24.389, 36.645, P = 0.001）. Conclusion AKT/mTOR signaling pathway is upregulated during COPD exacerbation. AKT inhibitor MK-2206 reduces AKT/mTOR pathway expression and may affect lung fibroblast and monocyte-derived macrophage migration, potentially playing a crucial role in COPD exacerbation process.
- Peripheral blood mononuclear cells,
- Akt/mTOR,
- Chronic obstructive pulmonary disease

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