Drake Li Y, Pfeffer-Kleemann Daniel, Zhang Emily Y, Koloko Ngassie Maunick Lefin, Pabelick Christina M, Prakash Y S
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
Am J Physiol Lung Cell Mol Physiol. 2025 Aug 1;329(2):L296-L306. doi: 10.1152/ajplung.00070.2025. Epub 2025 Jul 16.
Preterm infants frequently require respiratory support, including continuous positive airway pressure (CPAP), that imposes mechanical stretch on highly compliant perinatal airways. How this excess stress impacts airway development and function is not completely understood. Using human fetal airway smooth muscle (fASM), a key cell type in airway contractility and remodeling, as a model, we investigated the effects of stretch, focusing on the role of mechanosensitive ion channels Piezo1 and Piezo2. We found that CPAP-like static stretch did not alter Piezo1 and Piezo2 protein expression per se and had a minimal effect on fASM cell proliferation or IL-6 production during the stretch period. However, CPAP-like stretch produces long-term effects in fASM, leading to increased cell proliferation and IL-6 production during the poststretch period, though interestingly, it does not enhance extracellular matrix deposition. The role of Piezo channels appears context-dependent in that the Piezo1 antagonist GsMTx4 reduced baseline proliferation in nonstretched cells but slightly increased proliferation in stretched cells. Piezo1 and Piezo2 inhibition did not alter IL-6 production. These results suggest that stretch induces a sustained increase in cell proliferation and inflammatory responses, which may contribute to long-term remodeling in former preterm infants initially exposed to CPAP. Mechanical stretch associated with respiratory support can impair airway development and function in neonates, but the mechanisms are not fully understood. Using developing human airway smooth muscle cells exposed to cyclic forces with static stretch to mimic continuous positive airway pressure, we found that stretch dysregulates long-term cell proliferation and inflammatory cytokine production, and mechanosensitive Piezo ion channels may play a role in the proliferation response.
早产儿经常需要呼吸支持，包括持续气道正压通气（CPAP），这会对顺应性高的围产期气道施加机械牵张。这种过度应激如何影响气道发育和功能尚不完全清楚。我们以人胎儿气道平滑肌（fASM）（气道收缩和重塑中的关键细胞类型）为模型，研究牵张的影响，重点关注机械敏感离子通道Piezo1和Piezo2的作用。我们发现，类似CPAP的静态牵张本身不会改变Piezo1和Piezo2蛋白表达，并且在牵张期间对fASM细胞增殖或白细胞介素-6（IL-6）产生的影响最小。然而，类似CPAP的牵张在fASM中产生长期影响，导致牵张后时期细胞增殖增加和IL-6产生增加，不过有趣的是，它不会增强细胞外基质沉积。Piezo通道的作用似乎取决于具体情况，因为Piezo1拮抗剂GsMTx4降低了未牵张细胞的基线增殖，但略微增加了牵张细胞的增殖。抑制Piezo1和Piezo2不会改变IL-6的产生。这些结果表明，牵张诱导细胞增殖和炎症反应持续增加，这可能导致最初接受CPAP治疗的前早产儿出现长期重塑。与呼吸支持相关的机械牵张会损害新生儿气道发育和功能，但其机制尚不完全清楚。我们使用发育中的人气道平滑肌细胞，通过静态牵张使其暴露于周期性力来模拟持续气道正压通气，发现牵张会失调长期细胞增殖和炎性细胞因子产生，并且机械敏感的Piezo离子通道可能在增殖反应中发挥作用。
