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Am J Physiol Gastrointest Liver Physiol (October 29, 2009). doi:10.1152/ajpgi.90706.2008
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Research Article

Roles of Stem Cell Factor on the Depletion of Interstitial Cells of Cajal in the Colon of Diabetic Mice

Lin Lin,1 Li-ming XU,2 Wei Zhang,3 Ying-bin GE,4 Yu-rong TANG,2 Hong-jie ZHANG,2 Xue-liang LI,2 and Jiande D.Z. Chen5,*

1The First Affiliated Hospital of 2 3The First Affiliated Hospital of Nanjing Medical University 4Nanjing Medical University 5University of Texas Medical Branch

Submitted 18 December 2008 ; revision received 19 October 2009 ; accepted in final form 19 October 2009

ABSTRACT

The aim of this study was to investigate the effects of stem cell factor (SCF) on ICC depletion in the colon of diabetic mice. Male C57/BL6 mice were treated by a single dose intraperitoneal injection of Streptozotocin (STZ), and those displayed sustained high blood glucose were selected as diabetes mellitus (DM) models. Six groups of mice were used: three groups of normal non-diabetic mice (untreated and treated with IgG or SCF antibody), and three gourps of diabetic mice (untreated and treated with vehicle or SCF. Changes of the ICC quantities were analyzed by immunohistochemistry. ICC morphologies were observed with transmission electron microscopy. The SCF levels in sera and colon tissues were detected by ELISA and Western Blot respectively. The non-diabetic mice treated with SCF antibody and the untreated diabetic mice showed decreased SCF levels in the sera and colonic tissues, reduced numbers of ICC and pathological changes of the ICC ultrastructures while the non-diabetic mice treated with mouse IgG showed no significant changes compared to the non-diabetic mice. The diabetic mice treated with exogenous SCF showed restored SCF levels in both sera and colon tissues, and improvement in the numbers of ICC and the damages of ICC ultrastructures while the vehicle control of diabetic mice showed no significant changes compared to the diabetic mice . The blood glucose remained high and unchanged with the treatment of SCF or vehicle in the diabetic mice. These results indicate that diabetic mice show a decline in the number of ICC and impairment in the ultrastructures of ICC, and these abnormalities are attributed to a deficiency in the endogenous SCF but not related to hyperglycemia. Exogenous SCF partially reverses the pathological changes of ICC in diabetic mice.

Diabetes mellitus; Gastrointestinal motility; Interstitial cells of Cajal (ICC); Stem cell factor


* University of Texas Medical Branch jianchen{at}utmb.edu






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