Nitric oxide hinders club cell proliferation through Gdpd2 during allergic airway inflammation

Author:

Yue Qing1,Li Kuan23,Song Zhaoyu1ORCID,Wang Qi2,Wang Jianhai23,Li Xue23,Li Yu23,Zhang Qiuyang23,Zhu Yu4,Chen Huaiyong1235ORCID

Affiliation:

1. Department of Basic Medicine, Haihe Clinical School Tianjin Medical University China

2. Department of Basic Medicine, Haihe Hospital Tianjin University China

3. Tianjin Key Laboratory of Lung Regenerative Medicine China

4. Department of Clinical Laboratory, Haihe Hospital Tianjin University China

5. Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine Tianjin Institute of Respiratory Diseases China

Abstract

Excessive nitric oxide (NO) is often observed in the airways of patients with severe asthma. Here, we show that the NO donor diethylamine NONOate impairs the proliferative capacity of mouse club cells and induces club cell apoptosis, cell cycle arrest, and alterations in lipid metabolism. Our data suggest that NO inhibits club cell proliferation via upregulation of Gdpd2 (glycerophosphodiester phosphodiesterase domain containing 2). During ovalbumin (OVA) challenge, apoptotic club cells are observed, but surviving club cells continue to proliferate. OVA exposure induces Gdpd2 expression; Gdpd2 knockout promotes the proliferation of club cells but inhibits goblet cell differentiation. Elimination of airway NO was found to inhibit goblet cell differentiation from club cells during OVA challenge. Our data reveal that excessive NO might be related to airway epithelial damage in severe asthma and suggest that blockade of the NO‐Gdpd2 pathway may be beneficial for airway epithelial restoration.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Tianjin City

Publisher

Wiley

Subject

General Biochemistry, Genetics and Molecular Biology

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