PPM1A as a key target of the application of Jiawei‑Maxing‑Shigan decoction for the attenuation of radiation‑induced epithelial‑mesenchymal transition in type II alveolar epithelial cells

Abstract

Radiation-induced lung tissue injury is an important reason for the limited application of radiotherapy on thoracic malignancies. Previously, we reported that administration of Jiawei-Maxing-Shigan decoction (JMSD) attenuated the radiation-induced epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs) via TGF-β/Smad signaling. The present study aimed to examine the role of protein phosphatase Mg 2+ /Mn 2+ -dependent 1A (PPM1A) in the anti-EMT activity of JMSD on AECs. The components in the aqueous extract of JMSD were identified by high-performance liquid chromatography coupled with electrospray mass spectrometry. Primary rat type II AECs were treated with radiation (60Co γ-ray at 8 Gy) and JMSD-medicated serum. PPM1A was overexpressed and knocked down in the AECs via lentivirus transduction and the effects of JMSD administration on the key proteins related to TGF-β1/Smad signaling were measured by western blotting. It was found that radiation decreased the PPM1A expression in the AECs and JMSD-medicated serum upregulated the PPM1A expressions in the radiation-induced AECs. PPM1A overexpression increased the E-cadherin level but decreased the phosphorylated (p-)Smad2/3, vimentin and α-smooth muscle actin (α-SMA) levels in the AECs. By contrast, the PPM1A knockdown decreased the E-cadherin level and increased the p-Smad2/3, vimentin and α-SMA levels in the AECs and these effects could be blocked by SB431542 (TGF-β1/Smad signaling inhibitor). JMSD administration increased the E-cadherin level and decreased the p-Smad2/3, vimentin and α-SMA levels in the AECs; however, these effects could be blocked by siPPM1A-2. In conclusion, PPM1A is a key target of JMSD administration for the attenuation of the radiation-induced EMT in primary type II AECs via the TGF-β1/Smad pathway.