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Int J Clin Exp Pathol 2012;5(6):569-580

Original Article
Keratinocyte growth factor up-regulates Interleukin-7 expression following intestinal
ischemia/reperfusion in vitro and in vivo

Yu-Jiao Cai, Wen-Sheng Wang, Hong-Ying Liang, Li-Hua Sun, Daniel H Teitelbaum, Hua Yang

Department of General Surgery, Xingqiao Hospital, Third Military Medical University, Chongqing, China; Department of Surgery, the University of
Michigan Medical School, Ann Arbor, Michigan

Received 30 May, 2012; Accepted 2 July, 2012; Epub July 29, 2012; Published August 15, 2012

Abstract: Background: Epithelial cell (EC)-derived Interleukin-7 (IL-7) plays a crucial role in control of neighboring intestinal intraepithelial
lymphocytes (IEL) development and homeostasis, and IEL derived keratinocyte growth factor (KGF) promotes intestinal epithelial growth, which
was regulated by EC-derived IL-7. On this basis, we hypothesize that there is a crosstalk between IELs and ECs, and KGF could regulate the
EC-derived IL-7 expression, which should be associated with the protective effects by KGF on intestinal injury. Methods: Histological evaluation
was performed in small intestine tissues of patients with intestinal obstruction and IL-7 expression was detected by immunofluorescence.
Intestinal epithelial cells (LoVo) and adult C57BL/6J mice undergoing ischemia/reperfusion injury were treated with recombinant KGF. KGF,
KGF receptor(KGFR) and IL-7 expressions were measured with western blot and immunofluorescence analysis. Results: IL-7 expression
increased in the mild ischemia while decreased in severe ischemia small intestinal tissues of patients with intestinal obstruction. KGF
expression significantly decreased while IL-7 expression increased early after acute intestinal I/R administration in a mouse model. KGF
treatment significantly increased the IL-7 expression both in vitro and in vivo, while when the KGFR was blocked, the findings above were
absent. In addition, our results showed changes of IL-7 expression at different stages after acute intestinal I/R administration, KGF treatment
significantly attenuated the decreasing of IL-7 expression caused by acute intestinal I/R. Conclusion: KGF could up-regulate the IL-7
expression both in vitro and in vivo through KGFR pathway, which should have associated with the protective effects of KGF in intestinal injury.

Keywords: Keratinocyte growth factor, Interleukin-7, ischemia/reperfusion, mouse, epithelial cells

Address all correspondence to:
Dr. Hua Yang
Department of General Surgery
Xinqiao Hospital, Third Military Medical University
Chongqing 400037, China.
Tel: 13668057773 (Cell) OR: (0086)23-687-55705 (Office)
E-mail: hyang@med.umich.edu OR: huayang@tmmu.edu.cn