Anti-fibrogenic effect of umbilical cord-derived mesenchymal stem cell conditioned media in human esophageal fibroblasts

Abstract

Abstract Esophageal fibrosis and strictures can develop due to caustic or radiation injuries. Umbilical cord–derived mesenchymal stem cells (UC-MSCs) are known to mitigate fibrosis in various organs. However, the potential effects of UC-MSCs on human esophageal fibrosis remain underexplored. This study investigated the anti-fibrogenic properties and mechanisms of UC-MSC-derived conditioned media (UC-MSC-CM) on human esophageal fibroblasts (HEFs). HEFs were treated with TGF-β1 and then co-cultured with UC-MSC-CM, and the expression levels of RhoA, myocardin related transcription factor A (MRTF-A), serum response factor (SRF), Yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) in the HEFs were measured. UC-MSC-CM suppressed TGF-β1-induced fibrogenic activation in HEFs, as evidenced by the downregulation of extracellular matrix components. UC-MSC-CM notably diminished the expression of RhoA, MRTF-A, and SRF triggered by TGF-β1. In TGF-β1-stimulated HEFs, UC-MSC-CM significantly decreased the nuclear localization of MRTF-A and YAP. Additionally, UC-MSC-CM significantly diminished the TGF-β1-induced nuclear expressions of YAP and TAZ, while concurrently enhancing the cytoplasmic presence of phosphorylated YAP, which was previously reduced by TGF-β1. Human UC-MSC-CM can potentially inhibit TGF-β1-induced fibrogenic activation in HEFs by targeting the Rho-mediated MRTF/SRF and YAP/TAZ pathways. Thus, UC-MSC-CM is a potential candidate for stem cell therapies for esophageal fibrosis.