Keratinocyte growth factor improves epithelial structure and function in a mouse model of intestinal ischemia/reperfusion

PLoS One. 2012;7(9):e44772. doi: 10.1371/journal.pone.0044772. Epub 2012 Sep 13.

Abstract

Background: Intestinal ischemia/reperfusion (I/R) induces the desquamation of the intestinal epithelium, increases the intestinal permeability, and in patients often causes fatal conditions including sepsis and multiple organ failure. Keratinocyte growth factor (KGF) increases intestinal growth, although little is known about KGF activity on intestinal function after intestinal I/R. We hypothesized that KGF administration would improve the intestinal function in a mouse model of intestinal I/R.

Methods: Adult C57BL/6J mice were randomized to three groups: Sham, I/R group and I/R+KGF group. Mice were killed on day 5, and the small bowel was harvested for histology, wet weight, RNA and protein content analysis. Epithelial cell (EC) proliferation was detected by immunohistochemistry for PCNA, and apoptosis was determined by TUNEL staining. The expressions of Claudin-1 and ZO-1 were detected by immunohistochemistry. Epithelial barrier function was assessed with transepithelial resistance (TER).

Results: KGF significantly increased the intestinal wet weight, contents of intestinal protein and RNA, villus height, crypt depth and crypt cell proliferation, while KGF resulted in the decrease of epithelial apoptosis. KGF also stimulated the recovery of mucosal structures and attenuated the disrupted distribution of TJ proteins. Moreover, KGF attenuated the intestinal I/R-induced decrease in TER and maintained the intestinal barrier function.

Conclusion: KGF administration improves the epithelial structure and barrier function in a mouse model of intestinal I/R. This suggests that KGF may have clinical applicability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Fibroblast Growth Factor 7 / therapeutic use*
  • Intestinal Mucosa / cytology
  • Intestines / injuries*
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / drug therapy*

Substances

  • Fibroblast Growth Factor 7

Grants and funding

This research was supported by the National Natural Science Foundation of China (No. 30973113; No. 81020108023; No. 81000830). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.