Skip to main content
Gut logoLink to Gut
. 1999 Jan;44(1):26–32. doi: 10.1136/gut.44.1.26

The effect of epidermal growth factor on brush border surface area and function in the distal remnant following resection in the rabbit

J Hardin 1, B Chung 1, E O'Loughlin 1, D Gall 1
PMCID: PMC1760064  PMID: 9862822

Abstract

Background—Epidermal growth factor (EGF) has been shown to increase intestinal absorptive surface area and transport function in normal animals. 
Aims—To examine the effect of EGF on absorptive surface area and brush border membrane function in a model of massive small bowel resection. 
Methods—New Zealand white rabbits were randomised into two groups: a resected group (60% proximal small bowel resection); and an unmanipulated control group. Distal remnant tissue was examined 10 and 21 days postsurgery. In separate experiments oral EGF (40 µg/kg/day) was administered to resected animals from days 3 to 8 and animals were studied on day 10. 
Results—Ten days postsurgery brush border surface area and total absorptive surface area were significantly increased in remnant tissue while brush border membrane vesicle (BBMV) glucose uptake was significantly decreased compared with controls. By 21 days brush border surface area returned to control levels though BBMV glucose uptake remained depressed. EGF treatment induced a further increase in brush border surface area in remnant intestine but did not alter BBMV glucose uptake. 
Conclusions—Surgical resection results in significant elevations in absorptive surface area coupled with a decrease in brush border membrane transport function distal to the site of anastomosis. EGF enhances glucose uptake in remnant intestine via recruitment of additional microvillus membrane into the brush border. 



Keywords: short gut; resection; surface area; brush border membrane

Full Text

The Full Text of this article is available as a PDF (134.0 KB).

Figure 1 .

Figure 1

Representative photomicrographs from the mid-villus region in (A) control, (B) resected, and (C) resected + EGF tissue. Tissue appeared ultrastructurally normal. Bar = 1 µm. 


Figure 2 .

Figure 2

Mid-villus brush border surface area measurements in tissue from 10 day control (n=26 photomicrographs obtained from three animals), 10 day resected (n=29 photomicrographs from three animals), resected + EGF (n=41 photomicrographs from three animals), 21 day control (n=40 photomicrographs from three animals), and 21 day resected (n=30 photomicrographs from three animals) animals. *p<0.001 compared with control; †p<0.05 compared with 10 day resected group. Data represent mean (SE). 


Figure 3 .

Figure 3

Total absorptive surface area in the distal ileum in 10 (n=11) and 21 (n=5) day control and resected animals (n=6) and resected + EGF animals (n=6) as assessed by equilibration of the fluorescent membrane probe TMA-DPH. *p<0.05 compared with control; **p<0.01 compared with control; †p<0.05 compared with 10 day resection. Data represent mean (SE). 


Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  2. Buret A., Gall D. G., Olson M. E. Growth, activities of enzymes in the small intestine, and ultrastructure of microvillous border in gerbils infected with Giardia duodenalis. Parasitol Res. 1991;77(2):109–114. doi: 10.1007/BF00935423. [DOI] [PubMed] [Google Scholar]
  3. Buret A., Hardin J., Olson M. E., Gall D. G. Adaptation of the small intestine in desert-dwelling animals: morphology, ultrastructure and electrolyte transport in the jejunum of rabbits, rats, gerbils and sand rats. Comp Biochem Physiol Comp Physiol. 1993 May;105(1):157–163. doi: 10.1016/0300-9629(93)90189-b. [DOI] [PubMed] [Google Scholar]
  4. Buret A., O'Loughlin E. V., Curtis G. H., Gall D. G. Effect of acute Yersinia enterocolitica infection on small intestinal ultrastructure. Gastroenterology. 1990 Jun;98(6):1401–1407. doi: 10.1016/0016-5085(90)91068-h. [DOI] [PubMed] [Google Scholar]
  5. Chaet M. S., Arya G., Ziegler M. M., Warner B. W. Epidermal growth factor enhances intestinal adaptation after massive small bowel resection. J Pediatr Surg. 1994 Aug;29(8):1035–1039. doi: 10.1016/0022-3468(94)90274-7. [DOI] [PubMed] [Google Scholar]
  6. Curtis G. H., Patrick M. K., Catto-Smith A. G., Gall D. G. Intestinal anaphylaxis in the rat. Effect of chronic antigen exposure. Gastroenterology. 1990 Jun;98(6):1558–1566. doi: 10.1016/0016-5085(90)91090-s. [DOI] [PubMed] [Google Scholar]
  7. DAHLQVIST A. METHOD FOR ASSAY OF INTESTINAL DISACCHARIDASES. Anal Biochem. 1964 Jan;7:18–25. doi: 10.1016/0003-2697(64)90115-0. [DOI] [PubMed] [Google Scholar]
  8. Davidson G. P., Gall D. G., Petric M., Butler D. G., Hamilton J. R. Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport. J Clin Invest. 1977 Dec;60(6):1402–1409. doi: 10.1172/JCI108901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dowling R. H., Booth C. C. Structural and functional changes following small intestinal resection in the rat. Clin Sci. 1967 Feb;32(1):139–149. [PubMed] [Google Scholar]
  10. Fedorak R. N., Cheeseman C. I., Thomson A. B., Porter V. M. Altered glucose carrier expression: mechanism of intestinal adaptation during streptozocin-induced diabetes in rats. Am J Physiol. 1991 Oct;261(4 Pt 1):G585–G591. doi: 10.1152/ajpgi.1991.261.4.G585. [DOI] [PubMed] [Google Scholar]
  11. Feldman E. J., Dowling R. H., McNaughton J., Peters T. J. Effects of oral versus intravenous nutrition on intestinal adaptation after small bowel resection in the dog. Gastroenterology. 1976 May;70(5 PT1):712–719. [PubMed] [Google Scholar]
  12. Freeman H. J., Ellis S. T., Johnston G. A., Kwan W. C., Quamme G. A. Sodium-dependent D-glucose transport after proximal small intestinal resection in rat. Am J Physiol. 1988 Sep;255(3 Pt 1):G292–G297. doi: 10.1152/ajpgi.1988.255.3.G292. [DOI] [PubMed] [Google Scholar]
  13. Goodlad R. A., Savage A. P., Lenton W., Ghatei M. A., Gregory H., Bloom S. R., Wright N. A. Does resection enhance the response of the intestine to urogastrone-epidermal growth factor in the rat? Clin Sci (Lond) 1988 Aug;75(2):121–126. doi: 10.1042/cs0750121. [DOI] [PubMed] [Google Scholar]
  14. Hardin J. A., Buret A., Meddings J. B., Gall D. G. Effect of epidermal growth factor on enterocyte brush-border surface area. Am J Physiol. 1993 Feb;264(2 Pt 1):G312–G318. doi: 10.1152/ajpgi.1993.264.2.G312. [DOI] [PubMed] [Google Scholar]
  15. Hinegardner R. T. An improved fluorometric assay for DNA. Anal Biochem. 1971 Jan;39(1):197–201. doi: 10.1016/0003-2697(71)90476-3. [DOI] [PubMed] [Google Scholar]
  16. Hines O. J., Bilchik A. J., Zinner M. J., Skotzko M. J., Moser A. J., McFadden D. W., Ashley S. W. Adaptation of the Na+/glucose cotransporter following intestinal resection. J Surg Res. 1994 Jul;57(1):22–27. doi: 10.1006/jsre.1994.1103. [DOI] [PubMed] [Google Scholar]
  17. Horváth K., Hill I. D., Devarajan P., Mehta D., Thomas S. C., Lu R. B., Lebenthal E. Short-term effect of epidermal growth factor (EGF) on sodium and glucose cotransport of isolated jejunal epithelial cells. Biochim Biophys Acta. 1994 Jun 30;1222(2):215–222. doi: 10.1016/0167-4889(94)90171-6. [DOI] [PubMed] [Google Scholar]
  18. Kelly M., Butler D. G., Hamilton J. R. Transmissible gastroenteritis in piglets: a model of infantile viral diarrhea. J Pediatr. 1972 Jun;80(6):925–931. doi: 10.1016/S0022-3476(72)80003-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Lange Y., Swaisgood M. H., Ramos B. V., Steck T. L. Plasma membranes contain half the phospholipid and 90% of the cholesterol and sphingomyelin in cultured human fibroblasts. J Biol Chem. 1989 Mar 5;264(7):3786–3793. [PubMed] [Google Scholar]
  21. Malo C., Berteloot A. Analysis of kinetic data in transport studies: new insights from kinetic studies of Na(+)-D-glucose cotransport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus. J Membr Biol. 1991 Jun;122(2):127–141. doi: 10.1007/BF01872636. [DOI] [PubMed] [Google Scholar]
  22. Meddings J. B., Scott R. B., Fick G. H. Analysis and comparison of sigmoidal curves: application to dose-response data. Am J Physiol. 1989 Dec;257(6 Pt 1):G982–G989. doi: 10.1152/ajpgi.1989.257.6.G982. [DOI] [PubMed] [Google Scholar]
  23. Menge H., Murer H., Robinson J. W. Glucose transport by brush-border membrane vesicles after proximal resection or ileo-jejunal transposition in the rat. J Physiol. 1978 Jan;274:9–16. doi: 10.1113/jphysiol.1978.sp012130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Menge H., Sepúlveda F. V., Smith M. W. Cellular adaptation of amino acid transport following intestinal resection in the rat. J Physiol. 1983 Jan;334:213–223. doi: 10.1113/jphysiol.1983.sp014490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. O'Loughlin E., Winter M., Shun A., Hardin J. A., Gall D. G. Structural and functional adaptation following jejunal resection in rabbits: effect of epidermal growth factor. Gastroenterology. 1994 Jul;107(1):87–93. doi: 10.1016/0016-5085(94)90064-7. [DOI] [PubMed] [Google Scholar]
  26. Opleta-Madsen K., Hardin J., Gall D. G. Epidermal growth factor upregulates intestinal electrolyte and nutrient transport. Am J Physiol. 1991 Jun;260(6 Pt 1):G807–G814. doi: 10.1152/ajpgi.1991.260.6.G807. [DOI] [PubMed] [Google Scholar]
  27. Playford R. J., Marchbank T., Calnan D. P., Calam J., Royston P., Batten J. J., Hansen H. F. Epidermal growth factor is digested to smaller, less active forms in acidic gastric juice. Gastroenterology. 1995 Jan;108(1):92–101. doi: 10.1016/0016-5085(95)90012-8. [DOI] [PubMed] [Google Scholar]
  28. Playford R. J., Woodman A. C., Clark P., Watanapa P., Vesey D., Deprez P. H., Williamson R. C., Calam J. Effect of luminal growth factor preservation on intestinal growth. Lancet. 1993 Apr 3;341(8849):843–848. doi: 10.1016/0140-6736(93)93057-8. [DOI] [PubMed] [Google Scholar]
  29. Schulzke J. D., Fromm M., Bentzel C. J., Zeitz M., Menge H., Riecken E. O. Ion transport in the experimental short bowel syndrome of the rat. Gastroenterology. 1992 Feb;102(2):497–504. doi: 10.1016/0016-5085(92)90096-h. [DOI] [PubMed] [Google Scholar]
  30. Shepherd R. W., Gall D. G., Butler D. G., Hamilton J. R. Determinants of diarrhea in viral enteritis. The role of ion transport and epithelial changes in the ileum in transmissible gastroenteritis in piglets. Gastroenterology. 1979 Jan;76(1):20–24. doi: 10.1016/S0016-5085(79)80122-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sigalet D. L., Lees G. M., Aherne F., Van Aerde J. E., Fedorak R. N., Keelan M., Thomson A. B. The physiology of adaptation to small bowel resection in the pig: an integrated study of morphological and functional changes. J Pediatr Surg. 1990 Jun;25(6):650–657. doi: 10.1016/0022-3468(90)90356-e. [DOI] [PubMed] [Google Scholar]
  32. Thompson J. S., Bragg L. E., Saxena S. K. The effect of intestinal resection and urogastrone on intestinal regeneration. Arch Surg. 1990 Dec;125(12):1617–1621. doi: 10.1001/archsurg.1990.01410240099020. [DOI] [PubMed] [Google Scholar]
  33. VENABLE J. H., COGGESHALL R. A SIMPLIFIED LEAD CITRATE STAIN FOR USE IN ELECTRON MICROSCOPY. J Cell Biol. 1965 May;25:407–408. doi: 10.1083/jcb.25.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vanderhoof J. A., Langnas A. N., Pinch L. W., Thompson J. S., Kaufman S. S. Short bowel syndrome. J Pediatr Gastroenterol Nutr. 1992 May;14(4):359–370. doi: 10.1097/00005176-199205000-00001. [DOI] [PubMed] [Google Scholar]
  35. Zeitz M., Menge H., Riecken E. O. Early ultrastructural adaptive changes of ileal enterocytes after proximal small bowel resection as determined morphometrically. Res Exp Med (Berl) 1985;185(4):259–268. doi: 10.1007/BF01851950. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES