Has2 Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice

is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified as a candidate gene for increased susceptibility to adult asthma. However, whether dysfunction affects airway remodeling and steroid insensit...

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Bibliographic Details
Published in:Frontiers in immunology 2022-01, Vol.12, p.770305-770305
Main Authors: Sherpa, Mingma Thsering, Kiwamoto, Takumi, Matsuyama, Masashi, Tsunoda, Yoshiya, Yazaki, Kai, Yoshida, Kazufumi, Nakajima, Masayuki, Matsuno, Yosuke, Morishima, Yuko, Ishii, Yukio, Hizawa, Nobuyuki
Format: Article
Language:English
Subjects:
airway remodeling
Airway Remodeling - drug effects
Airway Remodeling - genetics
Airway Remodeling - immunology
Animals
asthma
Asthma - chemically induced
Asthma - genetics
Asthma - immunology
Drug Resistance - genetics
Drug Resistance - immunology
ER stress response
HAS2
Hyaluronan Synthases - genetics
Hyaluronan Synthases - immunology
IL-17
Immunology
Mice
Mice, Knockout
Ovalbumin - toxicity
Steroids - pharmacology
TGF-β1
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Summary:is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified as a candidate gene for increased susceptibility to adult asthma. However, whether dysfunction affects airway remodeling and steroid insensitivity is still limited. Therefore, this study aimed to clarify the dysfunction, triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. heterozygous-deficient ( ) mice and their wild-type littermates have been evaluated in a model of chronic ovalbumin (OVA) sensitization and challenge. Mice present a higher sensitivity to OVA and higher IL-17 release as well as eosinophilic infiltration. RNA sequencing demonstrated the downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in -OVA mice. The combined treatment with anti-IL-17A antibody and dexamethasone reduces steroid insensitivity in -OVA mice. attenuation worsens eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling and could potentially be exploited for their therapeutic benefits in patients with asthma.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.770305