Mesenchymal stem cells therapy ameliorates esophageal dysmotility in gastroesophageal reflux disease by modulating smooth muscle contractility, alleviating senescence by targeting the DNMT3a-HIF1α axis

Figure 6 Mesenchymal stem cells modulate contraction-related proteins through DNA methyltransferase 3a and hypoxia-inducible factor 1 alpha pathway. This figure explores the molecular pathways by which mesenchymal stem cells modulate contraction-related proteins. A: Time-dependent mRNA expression levels of DNA methyltransferase 3a (DNMT3a) and hypoxia-inducible factor 1 alpha (HIF1α), likely as line graphs; B and C: Western blot images and quantification for DNMT3a and HIF1α protein levels in human esophageal smooth muscle cells (HESMCs), respectively; D: Western blot images and quantification for alpha-smooth muscle actin, anoctamin 1, calcium voltage-gated channel subunit alpha1 C, myosin light chain kinase, phosphorylated-myosin light chain kinase, ratio analysis, myosin phosphatase target subunit 1, phosphorylated-myosin phosphatase target subunit 1, ratio analysis in HESMCs with HIF1α overexpression; E: Western blot images and quantification for myosin light chain kinase, myosin phosphatase target subunit 1, and alpha-smooth muscle actin in HESMCs treated with a DNMT3a inhibitor. Error bars represent SEM. ^cP < 0.001 vs control; ^gP < 0.001 vs gastroesophageal reflux disease model group. TNF: Tumor necrosis factor; MSC: Mesenchymal stem cell; Ctr: Control; GM: Gastroesophageal reflux disease model; α-SMA: Alpha-smooth muscle actin; MYLK: Myosin light chain kinase; p-MYLK: Phosphorylated-myosin light chain kinase; MYPT1: Myosin phosphatase target subunit 1; p-MYPT1: Phosphorylated-myosin phosphatase target subunit 1; ANO1: Anoctamin 1; CACNA1C: Calcium voltage-gated channel subunit alpha1 C; DNMT3a: DNA methyltransferase 3a; HIF1α: Hypoxia-inducible factor 1 alpha.