The Stimulatory Effect of Porcine Placenta Extract on in vitro Biological Activities of Keratinocytes and Fibroblasts

        Porcine placenta extract (PPE), a synergistic bioactive compound, enhances cellular functions such as proliferation, migration, and cellular signaling. Keratinocytes and fibroblasts play essential roles during wound healing, particularly in tissue regeneration. However, the direct impact of PPE on biological activities of keratinocytes and fibroblasts remains underexplored. This study aimed to elucidate the stimulatory impact of PPE on the proliferation, migration, and gene expression of matrix metalloproteinases (MMPs) and extracellular matrix (ECM)-related proteins in human keratinocytes and fibroblasts. Human keratinocyte (HaCaT) and fibroblast cell lines (Hs 895.Sk) were treated with specific concentrations of PPE (2.5, 5, 10, 12.5, 15, and 50 µg/mL). Cell proliferation and migration were assessed using MTT and scratch assays, respectively. Quantitative real-time PCR was performed to evaluate the expression of MMPs and ECM-related genes. Western blot was employed to investigate the activation of ERK1/2, AKT, JNK signaling pathways, and cyclin D1 expression. PPE significantly promoted the keratinocyte/fibroblast proliferation and migration in a concentration-dependent manner via activation of ERK1/2, AKT, and JNK signaling pathway. PPE also markedly upregulated the expression of MMP-2, MMP-10, and MMP-14 both in keratinocytes and fibroblasts, as well as α-SMA, fibronectin, collagen I, and collagen III in fibroblasts. Porcine placenta extract (PPE) enhances keratinocyte and fibroblast proliferation/migration by activating JNK, ERK1/2, and PI3K/AKT signaling pathways. PPE also upregulates MMP-and ECM-related gene expression including myofibroblast differentiation.