Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro

Abstract

Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. Methods: TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. Results: BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells. Conclusion:These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body

“…Similar to TGF-β-induced JNK/p38 activation, in the SMAD-independent mechanism, ubiquitinated TRAF6 stimulates PI3K/AKT signaling and induces ubiquitination and activation of AKT ( Yang et al, 2009 ). Although its specific function in fibrotic diseases is unclear, increasing evidence suggests that PI3K/AKT signaling plays a critical role in profibrotic processes in organs such as the liver, the heart, the kidney, the lungs, skin, and even oral mucosa ( Dai et al, 2015 ; Li et al, 2017 ; Chaigne et al, 2019 ; Mi et al, 2019 ; Wang et al, 2019a ; Zhou et al, 2019 ; Yin et al, 2020 ).…”

Pterostilbene alleviates pulmonary fibrosis by regulating ASIC2

“…TGF-β1 is considered the master profibrotic cytokine in the process of fibrosis, which is commonly used to induce cellular pulmonary fibrosis to establish an in vitro IPF model [ 29 , 30 ]. TGF-β1 can stimulate the abnormal proliferation of lung fibroblasts, promote the formation of myofibroblasts and activation of pro-fibrotic gene, leading to excessive accumulation of ECM between the lung interstitium and alveoli [ 31 ].…”

Qishen Huanwu capsule reduces pirarubicin-induced cardiotoxicity in rats by activating the PI3K/Akt/mTOR pathway

“…The PI3K/Akt pathway is one of the most important upstream pathways of mTOR (14). Buyang Huanwu decoction, the basic prescription of QSHWC, upregulates the PI3K/Akt pathway (15). In our previous study, network pharmacology was used to predict the mechanism by which QSHWC reduced the toxicity of anthracyclines.…”