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

Lu,Jinhua; Lin,Shengyou; Lin,Zechen; Lin,Xianlei; Shen,Yuezhong; Su,Jingyang

doi:10.3892/mmr.2021.12465

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

Authors:
- Jinhua Lu
- Shengyou Lin
- Zechen Lin
- Xianlei Lin
- Yuezhong Shen
- Jingyang Su
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Affiliations: Oncology Department, Dingqiao Branch of GuangXing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, P.R. China, Oncology Department, GuangXing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, P.R. China, Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, P.R. China
Published online on: September 24, 2021 https://doi.org/10.3892/mmr.2021.12465
Article Number: 825
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 Mg²⁺/Mn²⁺‑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.

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