The School of Life Sciences has made important progress in the mechanism of respiratory toxicity of PM2.5

Fine particulate matter (PM2.
5) pollution in the atmosphere is known to have health hazards and can promote the development of
respiratory diseases such as COPD, bronchitis and asthma.
Epidemiological investigation confirmed that the asymmetric dimethylarginine ADMA in plasma of patients with the above respiratory diseases was significantly increased, which could promote the occurrence and development of the disease by inhibiting nitric oxide synthase activity and
enhancing airway inflammation.
DDAH1, a key enzyme that degrades ADMA in vivo, exhibits significant protective effects
in animal models associated with respiratory diseases.
However, it is unclear
whether ADMA/DDAH1 is involved in lung damage caused by PM2.
5 exposure.
Lu Zhongbing and Ding Wenjun's research group of the College of Life Sciences have confirmed that PM2.
5 exposure can increase the content of ADMA in serum, while knocking out DDAH1 or supplementing with exogenous ADMA can promote it PM2.
5 exposure causes lung damage
.
The research paper was published online on October 14, 2022 in Particle and Fibre Toxicology, an authoritative journal of toxicology, with the title of the article Dimethylarginine dimethylaminohydrolase 1 protects PM2.
5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress
。

The study first found low-concentration PM2.
5 exposure (mean ~50 μg/^m3) and acute high-concentration PM2.
5 at 3-6 months in wild-type mice Exposure (~1500 μg/^m3) increased the amount
of ADMA in mouse serum.
Then, the study used DDAH1 gene knockout and transgenic mice to confirm that the deletion of DDAH1 significantly promoted lung damage caused by chronic PM2.
5 exposure, and aggravated lung fibrosis, vascular muscularization, inflammation, oxidative stress and apoptosis.
Overexpression of DDAH1 significantly alleviated PM2.
5-induced lung damage
.
Then, the study confirmed in a mouse model of acute exposure to PM2.
5 that the addition of exogenous ADMA also promoted pulmonary fibrosis, inflammation, oxidative stress and apoptosis
caused by PM2.
5.
Mechanistic studies have found that knocking out DDAH1 or supplementing ADMA can promote the activation of NF-κB and upregulate the expression of iNOS.
and reduce the expression
of endogenous antioxidant proteins SOD1 and PRDX4.
The study also elucidated the role of iNOS in macrophages in ADMA promoting PM2.
5-induced inflammation and oxidative stress.

Junling Gao, a doctoral student in the School of Life Sciences, and Lei Tong and Wang Hongyun, who have graduated, are the joint first authors
of this paper.
Professor Lu Zhongbing and Professor Ding Wenjun are the corresponding authors
of the paper.
The paper was supported
by the National Natural Science Foundation of China and the University of Chinese Academy of Sciences Excellent Teacher Improvement Program.
The paper is linked below

https://particleandfibretoxicology.
biomedcentral.
com/articles/10.
1186/s12989-022-00505-7

Mechanism of ADMA/DDAH1 pathway in PM2.
5-induced lung injury in mice