Long Noncoding RNA GAS5 Contributes to <i>Mycoplasma pneumoniae</i> Pneumonia by Regulating NF-<i>κ</i>B via miR-29c/HMGB1 Axis

Long Noncoding RNA GAS5 Contributes to Mycoplasma pneumoniae Pneumonia by Regulating NF-κB via miR-29c/HMGB1 Axis

Juhua Ji,^1,2 Fei Hong,² Yi Liu,³ Xiaobin Chu,² Lei Song,² Meijun Zhu,² Yan Lu² and Chuangli Hao¹

¹Department of Respiratory Diseases, Children’s Hospital of Soochow University, Suzhou, China
²Department of Pediatrics, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, China
³Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, China

Mycoplasma pneumoniae pneumonia (MPP) poses a major threat to pediatric health. Our previous study suggested that GAS5 level was elevated in the peripheral blood of MPP children. However, the mechanism by which GAS5 regulates lung inflammation Mycoplasma pneumoniae (MP) infection-induced remains unknown. An MPP mouse model was constructed by MP intranasal injection to enrich for alveolar macrophage (AM). Mouse AM was stimulated using lipid-associated membrane proteins (LAMPs) to mimic an in vitro pneumonia model, and transfection was used to achieve specific knockdown or overexpression of target genes. GAS5 level was significantly increased in AM of the MPP mouse model, and significantly and positively related with the mRNA level of HMGB1, but no physical binding between GAS5 and HMGB1 proteins. miR-29c level was significantly decreased in AM of the MPP mouse model and negatively related with the HMGB1. We found the specific binding of GAS5 to miR-29c, and the specific binding of miR-29c to the HMGB1 mRNA 3’UTR. miR-29c mimic and knockdown of HMGB1 both significantly impeded LAMPs-induced apoptosis, IL-6 and TNF-α secretion, and the NF-κB activation. Ectopic expression of GAS5 counteracted the effect of miR-29c mimic, and miR-29c inhibitor counteracted the effect of HMGB1 knockdown. Furthermore, silencing of GAS5 significantly alleviated MPP-induced inflammation and pathological lung injury in the MPP mouse model. GAS5/miR-29c/HMGB1 is highly involved in inflammation and lung histopathological injury in MPP disease progression by regulating the NF-κB signaling pathway.

Key words —— GAS5; HMGB1; miR-29c; Mycoplasma pneumoniae pneumonia; NF-κB signaling pathway

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Tohoku J. Exp. Med., 2024 December, 264(4), 193-202.

Correspondence: Chuangli Hao, Department of Respiratory Diseases, Children’s Hospital of Soochow University, No. 92, Zhongnan Street, Wuzhong District, Suzhou, Jiangsu 215002, China.

e-mail: hcl_md@sina.com