High-Content Screening of Wind-Dampness Dispelling Traditional Chinese Medicines against Podocyte EMT Induced by IgA1.

Aims: Immunoglobulin A (IgA) Nephropathy (IgAN) is characterized by pIgA1 deposition in the glomerular mesangium, resulting in podocyte Epithelial-to-Mesenchymal Transition (EMT). Traditional Chinese Medicines (TCMs) have been used for the treatment of IgAN for several years and have demonstrated positive efficacy. The present study aimed to establish a High-Content Screening (HCS) method for identifying wind-dampness dispelling TCM extracts that can mitigate podocyte EMT induced by pIgA1.

Material and methods: IgA1 from IgAN patients was used to establish a podocyte EMT model. The expression of EMT markers, including desmin, podocalyxin, and podocin, was assessed by Immunocytofluorescence (IF). An image-based HCS method was established to identify winddampness dispelling TCMs with the anti-EMT activity of podocyte EMT by automatic acquisition and processing of dual-fluorescent labeled images.

Results: A total of 21 wind-dampness-dispelling TCM extracts were screened using the HCS system, leading to the identification of eight wind-dampness-dispelling TCM extracts exhibiting anti-EMT activity. These eight extracts inhibited the pIgA-induced expression of desmin while upregulating the expression of podocalyxin and podocin.

Conclusion: By quantifying the changes in the expression of EMT markers during pIgA1- induced EMT, this study successfully identified wind-dampness dispelling TCM extracts with anti-EMT properties using an HCS system. In addition, the proposed approach presents a novel avenue for the identification of wind-dampness-dispelling TCMs for the treatment of pIgA1- induced EMT.