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PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model

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Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (PGZ) exhibits potential protective effects in asthma. Recently, regulator of G protein 4 (RGS4) has been reported to be associated with immunological and inflammatory responses. However, no evidence has shown the influence of PPARγ on RGS4 expression in airway disorders. In this study, BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge for 90 days to establish a chronic asthma mouse model. Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0.5 mg/kg) intratracheally. Invasive pulmonary function tests were performed 24 h after last challenge. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for further analyses after the mice were sacrificed. We found that PPARγ agonist PGZ administration significantly attenuated the pathophysiological features of OVA-induced asthma and increased the expression of RGS4. In addition, the attenuating effect of PGZ on airway inflammation, hyperresponsiveness (AHR), and remodeling was partially abrogated by administration of RGS4 inhibitor CCG 63802. We also found that the downregulation of RGS4 by CCG 63802 also significantly increased inflammatory cell accumulation and AHR, and increased levels of IL-4, IL-13, eotaxin, IFN-γ, and IL-17A in BALF, and total and OV-specific IgE in serum. Furthermore, the inhibitory effects of PGZ on the activations of ERK and Akt/mTOR signaling, and MMPs were apparently reversed by CCG 63802 administration. In conclusion, the protective effect of PGZ on OVA-induced airway inflammation and remodeling might be partly regulated by RGS4 expression through ERK and Akt/mTOR signaling.

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Funding

This work was funded by the Natural Science Foundation of China (No. 81000009), the Fundamental Research Funds for the Central Universities (2012jdhz15), and the Research Funds for the second affiliated hospital (RC (XM) 201101).

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Authors and Affiliations

  1. Respiratory Department, The Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine, 157 Xiwu Road, Xi’an, 710004, Shaanxi, China

    Xia Meng, Yonghong Zhang, Hongyang Shi, Wenjing Deng, Yanqin Liu, Ping Fang & Shuanying Yang

  2. Xi’an Children’s Hospital, 69 Xijuyuan Lane, Lianhu District, Xi’an, 710003, Shaanxi, China

    Xinrong Sun

  3. Respiratory Department, Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital, Xi’an Jiaotong University School of Medicine, 256 Youyi West Road, Xi’an, 710068, Shaanxi, China

    Guizuo Wang

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  1. Xia Meng
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  4. Hongyang Shi
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Correspondence to Ping Fang.

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All procedures performed in studies involving animals were in accordance with the Animal Research Ethics Committee of Xi’an Jiaotong University.

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Meng, X., Sun, X., Zhang, Y. et al. PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model. Inflammation 41, 2079–2089 (2018). https://doi.org/10.1007/s10753-018-0851-2

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  • DOI: https://doi.org/10.1007/s10753-018-0851-2

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