LincR-PPP2R5C Deficiency Alleviates Airway Remodeling by Inhibiting Epithelial-Mesenchymal Transition Through the PP2A/TGF-β1 Signaling Pathway in Chronic Experimental Allergic Asthma

Airway remodeling is a key characteristic of allergic asthma.

Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-β1, orchestrates airway remodeling.

Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-β1 production and EMT.

Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT.

Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma.

LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma.

Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice.

HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO.

Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-β1 production in epithelial cells.

In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-β1 signaling pathway.

Thus, lncRNAs, i.e., lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.