|
| Agents | Model | Molecular mechanism | Effect | Ref |
|
| Cigarette smoke (CS) | Baby hamster kidney (BHK) cells | CS induced CFTR internalization and insolubility | CS-induced CFTR dysfunction led to airway surface liquid dehydration | [13] |
| Endobronchial biopsy specimens | CS reduced lower airway CFTR activity in COPD patients | CS induced the acquired CFTR dysfunction contributing to COPD pathogenesis | [20] |
| HBECs | Induced CFTR dysfunction | ENaC inhibition partially restored CFTR function and mucus hydration in CB patients | [51] |
| Cigarette smoke condensate (CSC) | Primary MNSE and HSNE | CSC affects the calcium-activated Clā transport pathway | CSC impaired CFTR functions in epithelial cells | [52] |
| Cigarette smoke extract (CSE) | Primary HBECs | Cigarette smoking transmits acute reductions in CFTR | CFTR potentiator (VX-770) reversed CFTR function | [23] |
| Tobacco carcinogen NNK transporter MRP2 | Lung epithelial cells | Induced dysfunction of CFTR, MRP2, and PDZ proteins | Contributed to cigarette smoke-associated lung diseases, such as COPD and lung cancer | [53] |
| Roflumilast | Primary HBECs, Calu-3, and T84 monolayers | Roflumilast activated CFTR-mediated anion transport in airway and intestinal epithelia via a cAMP-dependent pathway | Roflumilast partially reversed the CS-impaired CFTR function and resulted in augmented ASL depth | [40] |
| Primary NHBE and Vero cell VC-10 | Roflumilast increased CFTR mRNA levels in CS-exposed cell cultures | Roflumilast can rescue smoke-induced mucociliary dysfunction by reversing decreased CFTR activity | [54] |
| HBECs | Roflumilast restored CFTR function in CS-exposed cells | Roflumilast combined with adenosine increased mucosal hydration in HBECs exposed to CS | [55] |
| 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) | Human lungs | Chronic exposure of CS led to endoplasmic reticulum stress, unfolded CFTR protein response, and cell apoptosis | CDDO corrected defective Nrf2-dependent cellular response in chronic exposure of CS-induced lung disease | [56] |
| miR-101 and miR-144 | HBECs and human lung tissues | Chronic exposure to CS upregulated miR-101 and miR-144, which suppressed CFTR in COPD lungs | miR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung | [57] |
| Ivacaftor, VX-770 | Primary HBECs | Cigarette smoking transmitted acute reductions in CFTR activity due to inhibition of CFTR-dependent fluid transport | Cigarette smoke-reduced mucus transport in smokers could be reversed by CFTR potentiator VX-770 | [23, 25] |
| Acrolein | Primary HBECs and A/J mice | Acrolein blocked CFTR by inhibiting channel gating | Acrolein mediated systemic CFTR dysfunction in smokers | [20] |
| Cadmium and manganese | 16HBE14o-cells and human COPD lung tissues | Cadmium and manganese of CS reduced levels of CFTR protein and mRNA | Accumulation of cadmium and manganese reduced CFTR expression in the lungs of patients with severe COPD | [31] |
| S-Nitrosoglutathione (GSNO) | The preclinical COPD-emphysemamurine model | Alleviated CS-induced acquired CFTR dysfunction, resulting in autophagy impairment | Increasing GSNO levels reduced CS-induced acquired CFTR dysfunction and controlled COPD emphysema pathogenesis | [17] |
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