The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma

Marc G. Jeschke, Ulrich Bolder, Celeste Finnerty, Rene Przkora, Ulla Müller, Rainer Maihöfer, James C. Thompson, Steven Wolf, David Herndon

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. Methods. Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 μg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. Results. Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-α and interleukin-1β, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. Conclusions. HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.

Original languageEnglish (US)
Pages (from-to)482-489
Number of pages8
JournalSurgery
Volume138
Issue number3
DOIs
StatePublished - Sep 2005

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Hepatocyte Growth Factor
Cell Proliferation
Apoptosis
Wounds and Injuries
Caspase 7
Epithelial Cells
Caspase 3
Hot Temperature
Serum
Liver Regeneration
Fas Ligand Protein
Mesentery
Interleukin-1
Small Intestine
Homeostasis
Tumor Necrosis Factor-alpha
Cytokines
Skin

ASJC Scopus subject areas

  • Surgery

Cite this

The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma. / Jeschke, Marc G.; Bolder, Ulrich; Finnerty, Celeste; Przkora, Rene; Müller, Ulla; Maihöfer, Rainer; Thompson, James C.; Wolf, Steven; Herndon, David.

In: Surgery, Vol. 138, No. 3, 09.2005, p. 482-489.

Research output: Contribution to journalArticle

Jeschke, Marc G. ; Bolder, Ulrich ; Finnerty, Celeste ; Przkora, Rene ; Müller, Ulla ; Maihöfer, Rainer ; Thompson, James C. ; Wolf, Steven ; Herndon, David. / The effect of hepatocyte growth factor on gut mucosal apoptosis and proliferation, and cellular mediators after severe trauma. In: Surgery. 2005 ; Vol. 138, No. 3. pp. 482-489.
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abstract = "Background. A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. Methods. Rats were pair-fed, underwent thermal trauma, and received saline (0.9{\%} NaCl; n = 28) or HGF (200 μg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. Results. Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-α and interleukin-1β, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. Conclusions. HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.",
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AU - Jeschke, Marc G.

AU - Bolder, Ulrich

AU - Finnerty, Celeste

AU - Przkora, Rene

AU - Müller, Ulla

AU - Maihöfer, Rainer

AU - Thompson, James C.

AU - Wolf, Steven

AU - Herndon, David

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N2 - Background. A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. Methods. Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 μg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. Results. Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-α and interleukin-1β, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. Conclusions. HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.

AB - Background. A severe burn injury is associated with an impairment of gut mucosal integrity and function, which is due to increases in small-bowel epithelial cell apoptosis and decreases in cell proliferation. Hepatocyte growth factor (HGF) was shown to improve regeneration in the liver, mesentery, and skin. The purpose of this study was to determine whether HGF can improve small-bowel homeostasis after injury and the cellular mechanisms by which these changes occur. Methods. Rats were pair-fed, underwent thermal trauma, and received saline (0.9% NaCl; n = 28) or HGF (200 μg/kg iv every 12 hours, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators, such as caspase-3 and caspase-7, Fas and Fas-ligand, Bcl-2, and Bax. In addition, serum cytokines were determined. Results. Gut epithelial cell apoptosis was increased in the saline and HGF groups after the thermal injury. Despite an increase in serum tumor necrosis factor-α and interleukin-1β, HGF did not affect small-bowel cell apoptosis, but it improved proliferation at days 1 and 2 after injury, which was associated with increased villous height and cell per villous, compared with saline controls, P < .05. Increased mucosal cell proliferation was associated with increased Bcl-2 in the HGF group, P < .05. HGF had no effect on apoptotic mediators, such as Fas, Fas-L, or caspase-3 and caspase-7. Conclusions. HGF improves small-bowel morphology after a severe burn by increasing mucosal Bcl-2 and, concomitantly, small-bowel epithelial cell proliferation.

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