Epithelial plasticity in COPD results in cellular unjamming due to an increase in polymerized actin

• Published in: Journal of cell science Vol. 135; no. 4
• Main Authors: Ghosh, Baishakhi, Nishida, Kristine, Chandrala, Lakshmana, Mahmud, Saborny, Thapa, Shreeti, Swaby, Carter, Chen, Si, Khosla, Atulya Aman, Katz, Joseph, Sidhaye, Venkataramana K
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15.02.2022
• Subjects: Actins - metabolism; Adhesion; Cell Biology and Disease; Cilia and Flagella; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - physiology; Humans; Microtubule Dynamics; Pulmonary Disease, Chronic Obstructive - metabolism; Smoke - adverse effects; Cellular unjamming; Cofilin-1; Polymerized actin; Epithelial plasticity; COPD; pEMT
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.258513

The airway epithelium is subjected to insults such as cigarette smoke (CS), a primary cause of chronic obstructive pulmonary disease (COPD) and serves as an excellent model to study cell plasticity. Here, we show that both CS-exposed and COPD-patient derived epithelia (CHBE) display quantitative evidence of cellular plasticity, with loss of specialized apical features and a transcriptional profile suggestive of partial epithelial-to-mesenchymal transition (pEMT), albeit with distinct cell motion indicative of cellular unjamming. These injured/diseased cells have an increased fraction of polymerized actin, due to loss of the actin-severing protein cofilin-1. We observed that decreasing polymerized actin restores the jammed state in both CHBE and CS-exposed epithelia, indicating that the fraction of polymerized actin is critical in unjamming the epithelia. Our kinetic energy spectral analysis suggests that loss of cofilin-1 results in unjamming, similar to that seen with both CS exposure and in CHBE cells. The findings suggest that in response to chronic injury, although epithelial cells display evidence of pEMT, their movement is more consistent with cellular unjamming. Inhibitors of actin polymerization rectify the unjamming features of the monolayer. This article has an associated First Person interview with the first author of the paper.