Abstract
Multiciliated airway epithelial cells possess motile cilia, which are essential for mucociliary clearance, facilitating the removal of particulates from the respiratory system. Previous studies showed that exposure to cigarette toxins causes damage to motile cilia formation, length, and function, and can lead to reduced mucociliary clearance and lung diseases like COPD. Given the limited options for treating smoking-related diseases, it is imperative to define novel therapeutics to address this need. Recently, we discovered that, contrary to its ability to depolymerize microtubules, the small molecule MI-181 can induce ciliogenesis and increase the length of primary cilia in retinal pigment epithelial cells without adverse effects on cell health. Here, we utilized a human airway basal stem cell derived air-liquid interface mucociliary airway epithelium model system, coupled with smoke exposure, to test the effect of MI-181 on motile cilia. We determined that MI-181 promotes the recovery of motile cilia length. Additionally, the effect of MI-181 on the area covered by motile cilia and levels of the FOXJ1 motile cilia transcription factor showed inter-donor heterogeneity. Importantly, transmission electron microscopy analysis of motile cilia axonemes showed that MI-181-treated motile cilia displayed a normal 9 + 2 arrangement of microtubules. Together, these data suggest that MI-181 promotes the recovery of motile cilia length after smoke exposure and that these cilia are structurally intact.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The accompanying Supplemental Material includes Supplemental Table S1.
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Fig. 1a was made with BioRender.
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This work was supported by the National Institutes of Health grants R35GM139539 to J.Z.T; T32GM145388 to T.V.G; T32ES015457 to C.C; and R01CA208303, U01HL175451, and U01HL153000 to B.N.G. Work was also supported by grants from the Tobacco-related Disease Research Program HIPRA 29IP-0597 and HIPA T31IR1637, DoD PR202868, and Burroughs Wellcome Fund 1020030 to B.N.G. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Institutes of Health.
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A.A.G., C.C., T.V.G., C.N., C.Z., B.N.G., and J.Z.T. initiated the project, designed experiments, wrote the manuscript, and analyzed results.
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MI-181 is the subject of patent number US 10,913,750 B; from The Regents of the University of California; authors: Jorge Torres, Robert Damoiseaux, Todd Yeates, Silvia Senese, Dan McNamara, and Yu-Chen Lo; related to its compositions and uses related thereto.
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Gholkar, A.A., Cherry, C., Gimeno, T.V. et al. MI-181 enhances ciliation and cilia length in a cigarette smoke exposed airway epithelial model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37296-2
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DOI: https://doi.org/10.1038/s41598-026-37296-2
