# Unraveling the Molecular Mechanisms Linking Cigarette Smoke Exposure to Skin Damage

## TL;DR

This study explores how cigarette smoke harms the skin at the molecular level, identifying key pathways and targets involved in the process.

## Contribution

The study integrates multiple approaches to uncover novel molecular mechanisms linking cigarette smoke exposure to skin damage.

## Key findings

- Cigarette smoke components interact strongly with key targets like STAT3, AKT1, and TP53.
- CS exposure in HaCaT cells reduced STAT3 and AKT expressions but increased p53, CASP3, and IL-6.
- PI3K-Akt, JAK-STAT, and p53 pathways are crucial in CS-induced skin damage and inflammation.

## Abstract

CS is an environmental pollutant everywhere, but we still do not fully know how it hurts our skin. This study integrates LC-MS, network toxicology, molecular docking, and experimental validation in order to understand how CS causes skin involvement at the molecular level. By searching a database, constructing a PPI network and analyzing GO/KEGG, we found 57 candidate targets related to CS-induced skin damage. We found that STAT3, AKT1, TP53, CASP3 and IL-6 play the core roles, and PI3K-Akt, p53, JAK-STAT and apoptosis pathways may be crucial. Molecular docking analysis confirmed strong interactions between components of CS and these key targets. In vitro validation using HaCaT cells showed that CS exposure decreased expressions of STAT3 and AKT, but increased p53, CASP3 and IL-6. The inhibition of PI3K-AKT- and JAK-STAT-related responses, coupled with the initiation of p53-driven apoptosis, led to the observed cytotoxicity, functional impairment, oxidative stress and inflammation, which induced and aggravated skin damage. These findings provide a new perspective on the harmful effects of CS on the skin, providing both a theoretical basis for strengthening regulatory measures to limit exposure and opening new avenues for exploring relevant prevention strategies.