Tripartite motif 22 interacts with protein phosphatase magnesium-dependent 1 A to aggravate radiation-induced epithelial-mesenchymal transition and fibrogenesis in lung epithelial cells.

Radiation-induced lung injury (RILI) is the damage to lung tissue caused by radiation. Epithelial-mesenchymal transition (EMT) and fibrogenesis in radiated lung epithelial cells play critical roles in RILI. Tripartite motif-containing (TRIM) family proteins have been shown to be involved in fibrotic diseases, but whether TRIM22 plays a role in RILI and relative underlying mechanism remain unexplored. Here, we reported a unique comprehensive analysis of the impact of TRIM22 on radiation-induced EMT and fibrogenesis in A549 and BEAS-2B cells. Cell viability and proliferation were measured by Cell-Counting Kit (CCK)-8 and colony formation assays. The interaction between TRIM22 and protein phosphatase magnesium-dependent 1 A (PPM1A) was validated using co-immunoprecipitation. A chromatin immunoprecipitation assay was used to verify the interaction between SMAD3 and TRIM22 promoter. Cell viability and proliferation were decreased by 8 Gy raddition. TRIM22 was elevated in a dose- and time-dependent manner after radiation, and its knockdown reduced EMT and fibrogenesis. TRIM22 could interact with PPM1A and promote its ubiquitination to activate the TGF-β1/Smad pathway. The overexpression of PPM1A abolished TRIM22-mediated EMT and fibrogenesis. Meanwhile, SMAD3 could bind to the TRIM22 promoter to elevate its expression. This study revealed a novel TRIM22/PPM1A/Smad3 signaling pathway that contributes to the raddition-induced EMT and fibrogenesis, which would provide novel targets and strategies for treating RILI.