Human umbilical cord mesenchymal stem cell-derived exosomes alleviate experimental colitis by maintaining the intestinal barrier and remodeling macrophage polarization

Figure 4 Human umbilical cord mesenchymal stem cell-derived exosomes upregulate the nuclear factor-erythroid 2 related factor 2/heme oxygenase-1/glutathione peroxidase 4 axis to reduce inflammation and oxidative stress. A-C: Routine whole blood parameters as indicators of systemic inflammation; D and E: Serum alanine aminotransferase and aspartate aminotransferase levels as markers of liver function; F: Hematoxylin-eosin staining of mouse spleen (5 ×, scale bar = 400 μm) and liver tissues (30 ×, scale bar = 200 μm); G and H: Activities of the antioxidant markers glutathione and superoxide dismutase in colon tissues; I: Protein expression levels of the nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) axis in mouse colon tissues; J-L: Quantitative analysis of protein expression of Nrf2, HO-1, and GPX4 by Western blot; M: Western blot analysis of Nrf2, HO-1, and GPX4 expression in RAW264.7 cells after human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Ex) treatment; N-P: Messenger RNA expression levels of Nrf2, HO-1, and GPX4 in mouse colon tissues; Q-S: Quantitative analysis of protein expression of Nrf2, HO-1, and GPX4 in RAW264.7 cells treated with hucMSC-Ex. ^aP < 0.05. ^bP < 0.01. ^cP < 0.001. NS: No significance; NC: Negative control; DSS: Dextran sulfate sodium; hucMSC-Ex: Human umbilical cord mesenchymal stem cell-derived exosomes; WBC: White blood cell; RBC: Red blood cell; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione; SOD: Superoxide dismutase; Nrf2: Nuclear factor-erythroid 2 related factor 2; HO-1: Heme oxygenase-1; GPX4: Glutathione peroxidase 4; M^PBS: Phosphate-buffered saline treatment; M^LPS: Lipopolysaccharide + interferon-γ treatment; M^IL-4: Interleukin-4 + interleukin-13 treatment; Ex: Exosomes; PBS: Phosphate-buffered saline.