Effect of PPARß/d agonist GW501516 on human and murine mesenchymal stromal cells
This study employed 3' RNA-Seq profiling (3RSP) to investigate the transcriptomic effects of the PPARß/d agonist GW501516 (1 µM, 24 hours) on mesenchymal stromal cells (MSCs). Treated samples were compared with untreated controls to identify differentially expressed genes. The analysis revealed ANGPTL4 as the most significantly overexpressed gene in the treated condition across multiple experimental models, including murine and human MSCs. Importantly, this upregulation was observed in human MSCs derived from diverse tissues, such as adipose tissue, bone marrow, and umbilical cord, highlighting the consistent response of MSCs to PPARß/d activation across species and sources. Further functional experiments demonstrated that ANGPTL4 plays a pivotal role in enhancing the anti-apoptotic properties of MSCs. This effect was evident in both autocrine (self-regulating) and paracrine (targeting other cells) mechanisms, suggesting that ANGPTL4 may act as a key mediator of MSC-based therapeutic effect. Overall design: Bone marrow murine MSC and human MSC (from bone marrow, adipose tissue and umbilical cord) were treated with GW501516 (1 uM) for 24 hours. Then, 3RSP profiling of control and PPAR agonist-treated cells was performed.