# MI-181 enhances ciliation and cilia length in a cigarette smoke exposed airway epithelial model

## TL;DR

MI-181 helps repair cilia in airway cells damaged by cigarette smoke, potentially offering a new treatment for smoking-related lung diseases.

## Contribution

MI-181 promotes recovery of motile cilia length and structural integrity in smoke-exposed airway epithelium.

## Key findings

- MI-181 increases motile cilia length in a cigarette smoke-exposed airway model.
- MI-181-treated cilia maintain a normal 9+2 microtubule structure as seen under electron microscopy.
- The drug's effects on cilia coverage and FOXJ1 levels vary between donors.

## 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.

The online version contains supplementary material available at 10.1038/s41598-026-37296-2.