Fig 2: Overexpression of Notch1 and Notch2 in the CPF group results in ectopic formation of PTs. (A) mRNA levels of NPC genes and (B) Notch1 and Notch2. n = 6. (C, D) Representative immunoblot images and quantification analysis of Notch1, Notch2, and Six2 of E18.5 kidneys. n = 6. (E) E18.5 kidney fluorescence detection of Lotus tetragonolobus lectin (LTL) binding (green) and Six2 (red), and immunohistochemistry for Aqp1. Scale bars: 100 µm. (F–H) Quantification of the LTL+ tubule numbers, Six2+ cell numbers, and Aqp1+ tubule numbers (n = 6). (I, J) The protein level of Aqp1 in E18.5 kidneys. n = 6. (K) Four- and 8-week immunofluorescence detection of LTL binding (green) and Aqp2 (red), and immunohistochemistry for Aqp1. Scale bars: 100 µm. (L–O) Quantification of LTL+ tubule numbers and Aqp1+ tubule numbers in 4- and 8-week kidneys for the two groups (n = 6). (P, Q) Serum creatinine and blood urea nitrogen levels of 4- and 8-week mice of the CPF group compared with DMSO controls. Mean ± SD from three to five experiments. ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05.

Fig 3: ADAM10 regulates Notch expression and promotes cell proliferation and migration in human 293T cells. (A, B) Effect of pcDNA3-ADAM10-HA plasmid on the protein levels of NOTCH1 (NTM), NOTCH2 (NTM), and HES1 (n = 6). (C–E) Immunofluorescence staining for NOTCH1 and NOTCH2 in 293T cells. The ratio of nuclear expression to total expression was analyzed using Imaris software (n = 3). Scale bars: 5 µm. (F, G) Effect of pcDNA3-ADAM10-HA plasmid on the cell proliferation index and migration index of 293T cells. (H, I) Effect of siRNA-ADAM10 and siRNA-ADAM17 on cell proliferation and migration of 293T cells.

Fig 4: Schematic diagram of the mechanisms underlying the protective anti-inflammatory effects of mechanical ventilation. Epithelial cells secrete exosomes containing miR-21a-5p, which are engulfed by macrophages. miR-21a-5p represses Notch2, which downregulates SOCS1, promoting M2 macrophage polarization. Thus, the communication between epithelial cells and macrophages involving exosomal miR-21a-5p exerts a protective effect during mechanical ventilation. SOCS1, suppressor of cytokine signaling 1.

Fig 5: Representative immunohistochemical patterns of an ICC developed in AKT/Jag1 mice. The tumour exhibits homogeneous immunoreactivity for Jag1 and activated/phosphorylated(p)-AKT, thus implying its origin from doubly transfected cells. CK19 staining is used as a biliary marker, ubiquitously positive in ICC lesions. In addition, the cholangiocellular lesion shows intense immunolabelling for markers of the Notch (Notch2, Hes1) and mTOR (phosphorylated/activated RPS6) pathways. The lesion is highly proliferating, as demonstrated by strong immunoreactivity for Ki67 staining. Original magnification: × 100.