Kaempferol Restores Cilia Length Through Axonemal Microtubule Stabilization.
- 1Department of Biomedical Engineering and Technology, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Abstract
Ciliary shortening disrupts cilium-dependent signaling and tissue homeostasis and contributes to diverse ciliopathies and acquired disorders. However, the underlying mechanisms and pharmacological strategies for restoring ciliary length remain poorly understood. Here, we identify Kaempferol (Kae) as a previously unrecognized small-molecule regulator of ciliary length. Transcriptomic profiling showed that Kae-responsive genes were enriched in cytoskeleton- and microtubule-related processes, including microtubule organization and motor protein activity, suggesting that cytoskeletal regulation may contribute to its effects on ciliary length. Further investigation demonstrated that Kae promoted ciliary elongation under basal conditions and restored ciliary length across mechanistically distinct defect models, including SARS-CoV-2 non-structural protein 13 (NSP13) expression, Ciliobrevin D-mediated dynein inhibition, and centrosomal protein 290 (CEP290) deficiency. Mechanistically, Kae enhanced microtubule stability, as indicated by increased acetylated α-tubulin (ACTUB) expression, greater resistance to nocodazole-induced depolymerization, and enhanced microtubule recovery. Consistent with these cellular effects, Kae promoted microtubule recovery and preserved ciliary ultrastructure in the NSP13-induced airway injury model in vivo. These findings establish Kae as a pharmacological modulator of ciliary length and highlight axonemal microtubule stabilization as a potential strategy for restoring dysfunctional cilia.
Related
- Cell-free reconstitution reveals synergistic stabilization of microtubule doublets by PACRG and FAP20
- Microtubule destabilization by SB225002 through preferential weakening of lateral tubulin interactions revealed by structural and computational analyses
- Dishevelled2 Condensates control Axon Initial Segment (AIS) assembly and function through MTCL1-Dependent microtubule recruitment
- An atlas of microtubule lattice parameters regulated through ligand binding to the microtubule-stabilizing sites
- Structural streamlining of axonemal doublet microtubules in Plasmodium male gametes
BibTeX
@article{dai2026kaempferol,
title = {{Kaempferol Restores Cilia Length Through Axonemal Microtubule Stabilization.}},
author = {Xuyao Dai and Yi Zhao and Ruodan Xu and Ning Li},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191806},
url = {https://europepmc.org/article/MED/42882504},
note = {CC BY},
}
RIS
TY - JOUR
TI - Kaempferol Restores Cilia Length Through Axonemal Microtubule Stabilization.
AU - Xuyao Dai
AU - Yi Zhao
AU - Ruodan Xu
AU - Ning Li
PY - 2026
DA - 2026/10/03
JO - Cells
DO - 10.3390/cells15191806
UR - https://europepmc.org/article/MED/42882504
AB - Ciliary shortening disrupts cilium-dependent signaling and tissue homeostasis and contributes to diverse ciliopathies and acquired disorders. However, the underlying mechanisms and pharmacological strategies for restoring ciliary length remain poorly understood. Here, we identify Kaempferol (Kae) as a previously unrecognized small-molecule regulator of ciliary length. Transcriptomic profiling showed that Kae-responsive genes were enriched in cytoskeleton- and microtubule-related processes, including microtubule organization and motor protein activity, suggesting that cytoskeletal regulation may contribute to its effects on ciliary length. Further investigation demonstrated that Kae promoted ciliary elongation under basal conditions and restored ciliary length across mechanistically distinct defect models, including SARS-CoV-2 non-structural protein 13 (NSP13) expression, Ciliobrevin D-mediated dynein inhibition, and centrosomal protein 290 (CEP290) deficiency. Mechanistically, Kae enhanced microtubule stability, as indicated by increased acetylated α-tubulin (ACTUB) expression, greater resistance to nocodazole-induced depolymerization, and enhanced microtubule recovery. Consistent with these cellular effects, Kae promoted microtubule recovery and preserved ciliary ultrastructure in the NSP13-induced airway injury model in vivo. These findings establish Kae as a pharmacological modulator of ciliary length and highlight axonemal microtubule stabilization as a potential strategy for restoring dysfunctional cilia.
SN - 2073-4409
ER -