Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.

Air-liquid interface culture; Carbon black; Molecular dynamics simulation; Respiratory exposure risk; ΔNp63.