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.

中文翻译：

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PPM1A作为应用加味麻杏石甘汤减缓Ⅱ型肺泡上皮细胞放射性上皮间质转化的关键靶点。

放射性肺组织损伤是胸部恶性肿瘤放疗应用受限的重要原因。此前，我们报道了加味麻杏石甘汤 (JMSD) 通过 TGF-β/Smad 信号传导减弱肺泡上皮细胞 (AECs) 中辐射诱导的上皮间质转化 (EMT)。本研究旨在检验蛋白磷酸酶 Mg ²⁺ /Mn ^{2+的作用。}- JMSD 对 AEC 的抗 EMT 活性中的依赖性 1A (PPM1A)。JMSD水提液中的成分采用高效液相色谱-电喷雾质谱联用进行鉴定。原代大鼠 II 型 AEC 接受放射治疗（60Co γ 射线，8 Gy）和 JMSD 含药血清。PPM1A 通过慢病毒转导在 AEC 中过表达并被敲低，通过蛋白质印迹测量 JMSD 对与 TGF-β1/Smad 信号传导相关的关键蛋白的影响。发现辐射降低了 AECs 中 PPM1A 的表达，而 JMSD 药物血清上调了辐射诱导的 AECs 中 PPM1A 的表达。PPM1A 过表达增加了 AEC 中的 E-钙粘蛋白水平，但降低了磷酸化 (p-)Smad2/3、波形蛋白和 α-平滑肌肌动蛋白 (α-SMA) 水平。相比之下，PPM1A 敲低降低了 E-cadherin 水平并增加了 AEC 中的 p-Smad2/3、波形蛋白和 α-SMA 水平，这些作用可以被 SB431542（TGF-β1/Smad 信号抑制剂）阻断。JMSD 给药增加了 AEC 中的 E-cadherin 水平并降低了 p-Smad2/3、波形蛋白和 α-SMA 水平；然而，这些影响可能会被 siPPM1A-2 阻止。总之，PPM1A 是 JMSD 给药的关键靶点，可通过 TGF-β1/Smad 通路减弱原发性 II 型 AEC 中辐射诱导的 EMT。这些影响可以被 siPPM1A-2 阻止。总之，PPM1A 是 JMSD 给药的关键靶点，可通过 TGF-β1/Smad 通路减弱原发性 II 型 AEC 中辐射诱导的 EMT。这些影响可以被 siPPM1A-2 阻止。总之，PPM1A 是 JMSD 给药的关键靶点，可通过 TGF-β1/Smad 通路减弱原发性 II 型 AEC 中辐射诱导的 EMT。