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AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy.METHODS Fibrinogen wild-type(Fib+/+), fibrinogen heterozygous(Fib+/-), and fibrinogen knockout(Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/-mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/-mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/-mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/-mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/-mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/-mice. Importantly, irradiated Fib-/-mice exhibited substantially less overall intestinal structural injury(RIS, P = 0.000002), intestinal wall thickness(P = 0.003), intestinal serosal thickness(P = 0.009), collagen deposition(P = 0.01), TGF-β immunoreactivity(P = 0.03), intestinal smooth muscle proliferation(P = 0.046), neutrophil infiltration(P = 0.01), and intestinal mucosal injury(P = 0.0003), compared to irradiated Fib+/+ and Fib+/-mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage.
AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib + / +), fibrinogen heterozygous (Fib +/-), and fibrinogen knockout (Fib- / -) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 weeks and 26 weeks after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib + / + and Fib +/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Thus, Fib +/- mice were used as littermate controls. Unlik no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib - / - mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib- / -mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib + / + and Fib +/- mice. Importantly, irradiated Fib - / - mice were substantially less overall intestinal structural injury (RIS, P = 0.000002) P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib + / + and Fib +/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestin al damage.