Figure 5.
Teduglutide treatment promotes KGF production and protects ISCs from GVHD. (A) Gene-expression array from BALB/c mice treated with teduglutide or vehicle from day −3 to day 10 shows increased expression of different growth factors, one of them is KGF (FGF7) in the teduglutide-treated mice in comparison with the control mice. Results are shown from 1 experiment. *Nonadjusted value of P < .05. (B) Relative expression of KGF analyzed on day 5 in the small intestine of BALB/c allo-HCT mice treated with teduglutide or vehicle compared with the untreated control mice (n = 11 per group). Mice were treated with teduglutide or vehicle from day −3 until day +3 unless differently specified. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (C) Quantification of primary intestinal organoids that were cultured for 2 days with different teduglutide concentrations reveals an increased surface area in the wells treated with 250 and 500 nM teduglutide when compared with the untreated cells. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (D) Representative microscopy images of mouse primary intestinal organoids. Figures indicate crypt cell proliferation in a dose-dependent manner upon teduglutide treatment in contrast to the untreated cells. Results are shown from 2 independent experiments. Scale bars, 50 µm. (E) Representative immunofluorescence stain images stained for Lgr5+ GFP-ISCs (green) taken on day 6 from allo-HCT B6-Lgr5-EGFPcreER reporter mice that were treated with vehicle or teduglutide from day −3 to day 3. Images indicate reduced Lgr5+ cells in mice with GVHD in comparison with the untreated control mice. In contrast, the teduglutide-treated mice exhibit an enhanced number of Lgr5+ cells during GVHD. (F) Quantification of Lgr5+ cells/crypt of untreated B6-Lgr5-EGFPcreER (n = 7) or B6-Lgr5-EGFPcreER mice that underwent allo-HCT and were treated with teduglutide or vehicle (n = 8 per group). Teduglutide treatment protects ISCs from their loss due to GVHD. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (G-H) qPCR-based quantification of the ISC markers Olfm4 and Prom-1 expression in small intestine from untreated (n = 10) or allo-HCT BALB/c mice on day 5 treated with vehicle or teduglutide (n = 16 per group). Data were pooled from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (I) Gene-expression array of ISC markers analyzed on day 10 from the small intestine of allo-HCT BALB/c mice treated with teduglutide or vehicle from day −3 to day 10. Experiment was performed once.

Teduglutide treatment promotes KGF production and protects ISCs from GVHD. (A) Gene-expression array from BALB/c mice treated with teduglutide or vehicle from day −3 to day 10 shows increased expression of different growth factors, one of them is KGF (FGF7) in the teduglutide-treated mice in comparison with the control mice. Results are shown from 1 experiment. *Nonadjusted value of P < .05. (B) Relative expression of KGF analyzed on day 5 in the small intestine of BALB/c allo-HCT mice treated with teduglutide or vehicle compared with the untreated control mice (n = 11 per group). Mice were treated with teduglutide or vehicle from day −3 until day +3 unless differently specified. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (C) Quantification of primary intestinal organoids that were cultured for 2 days with different teduglutide concentrations reveals an increased surface area in the wells treated with 250 and 500 nM teduglutide when compared with the untreated cells. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (D) Representative microscopy images of mouse primary intestinal organoids. Figures indicate crypt cell proliferation in a dose-dependent manner upon teduglutide treatment in contrast to the untreated cells. Results are shown from 2 independent experiments. Scale bars, 50 µm. (E) Representative immunofluorescence stain images stained for Lgr5+ GFP-ISCs (green) taken on day 6 from allo-HCT B6-Lgr5-EGFPcreER reporter mice that were treated with vehicle or teduglutide from day −3 to day 3. Images indicate reduced Lgr5+ cells in mice with GVHD in comparison with the untreated control mice. In contrast, the teduglutide-treated mice exhibit an enhanced number of Lgr5+ cells during GVHD. (F) Quantification of Lgr5+ cells/crypt of untreated B6-Lgr5-EGFPcreER (n = 7) or B6-Lgr5-EGFPcreER mice that underwent allo-HCT and were treated with teduglutide or vehicle (n = 8 per group). Teduglutide treatment protects ISCs from their loss due to GVHD. Results are shown from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (G-H) qPCR-based quantification of the ISC markers Olfm4 and Prom-1 expression in small intestine from untreated (n = 10) or allo-HCT BALB/c mice on day 5 treated with vehicle or teduglutide (n = 16 per group). Data were pooled from 2 independent experiments. The P values were calculated using the unpaired, 2-sided Student t test. (I) Gene-expression array of ISC markers analyzed on day 10 from the small intestine of allo-HCT BALB/c mice treated with teduglutide or vehicle from day −3 to day 10. Experiment was performed once.

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