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Epidermal Growth Factor Receptor Is Increased in Rabbit Intestinal Brush Border Membrane After Small Bowel Resection

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Abstract

A defective epidermal growth factor receptor (EGFR) abrogates adaptation, while overexpression of EGFR or exogenous epidermal growth factor (EGF) enhances adaptation following small bowel resection (SBR). EGFR is predominantly located on the enterocyte basolateral membrane, yet luminal EGF is increased in injured mucosa. We hypothesized that EGFR is both increased and redistributed to the enterocyte brush border membrane (BBM) after SBR and that parenteral EGF will reverse this redistribution. Rabbits (N = 20) were subjected to sham operation or SBR. EGF or vehicle were administrated one week postoperatively to SBR rabbits, and the gut was harvested one week later. EGFR levels in intestinal crude extracts and purified BBM were determined by Western blot analysis. No difference in EGFR level was detected in the crude extract among any of the groups. SBR more than doubled EGFR amount in BBM (P < 0.006). Parenteral EGF did not influence this redistribution. Thus, EGFR is partially redistributed to the BBM in the mucosa of SBR rabbits, and parenteral EGF does not reverse this redistribution.

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REFERENCES

  1. Wilmore DW, Byrne TA, Persinger RL: Short bowel syndrome: New therapeutic approaches. Curr Prob Surg 34:389-444, 1997

    Article  CAS  Google Scholar 

  2. Vanderhoof JA, Langnas AN: Short-bowel syndrome in children and adults. Gastroenterology 113:1767-1778, 1997

    Article  CAS  PubMed  Google Scholar 

  3. Helmrath MA, Erwin CR, Warner BW: A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation. J Sur Res 69:76-80, 1997

    Article  CAS  Google Scholar 

  4. Helmrath MA, Erwin CR, Shin CE, Warner BW: Adaptation after small bowel resection is enhanced in transgenic mice with targeted intestinal overexpression of EGF. Surg For 48:231-233, 1997

    CAS  Google Scholar 

  5. Goodlad RA, Wright NA: Epidermal growth factor (EGF). Baillie res Clin Gastroenterol 10:33-47, 1996

    Article  CAS  Google Scholar 

  6. Uribe JM, Barrett KE: Nonmitogenic actions of growth factors: An integrated view of their role in intestinal physiology and pathophysiology. Gastroenterology 112:255-268, 1997

    CAS  PubMed  Google Scholar 

  7. Iannoli P, Miller JH, Ryan CK, Gu LH, Ziegler TR, Sax HC: Epidermal growth factor and human growth hormone accelerate adaptation after massive enterectomy in an additive, nutrient-dependent, and site-specific fashion. Surgery 122:721-728; discussion 728-729, 1997

    Article  CAS  PubMed  Google Scholar 

  8. Iannoli P, Miller JH, Ryan CK, Gu LH, Ziegler TR, Sax HC: Human growth hormone induces system B transport in short bowel syndrome. J Sur Res 69:150-158, 1997

    Article  CAS  Google Scholar 

  9. Seydel AS, Miller JH, Sarac TP, Ryan CK, Chey WY, Sax HC: Octreotide diminishes luminal nutrient transport activity, which is reversed by epidermal growth factor. Am J Surg 172:267-271, 1996

    Article  CAS  PubMed  Google Scholar 

  10. Jansson JO, Ekberg S, Hoath SB, Beamer WG, Frohman LA: Growth hormone enhances hepatic epidermal growth factor receptor concentration in mice. J Clin Invest 82:1871-1876, 1988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Johansson S, Husman B, Norstedt G, Andersson G: Growth hormone regulates the rodent hepatic epidermal growth factor receptor at a pretranslational level. J Mol Endocrinol 3:113-120, 1989

    Article  CAS  PubMed  Google Scholar 

  12. Wiepz GJ, Houtman JC, Cha D, Bertics PJ: Growth hormone attenuation of epidermal growth factor-induced mitogenesis. J Cell Physiol 173:44-53, 1997

    Article  CAS  PubMed  Google Scholar 

  13. Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y, Kadowaki T: Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone. Nature 390:91-96, 1997

    Article  CAS  PubMed  Google Scholar 

  14. Hobert ME, Kil SJ, Medof ME, Carlin CR: The cytoplasmic juxtamembrane domain of the epidermal growth factor receptor contains a novel autonomous basolateral sorting determinant. J Biol Chem 272:32901-32909, 1997

    Article  CAS  PubMed  Google Scholar 

  15. Playford RJ, Hanby AM, Gschmeissner S, Peiffer LP, Wright NA, McGarrity T: The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract. Gut 39:262-266, 1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Scheving LA, Shiurba RA, Nguyen TD, Gray GM: Epidermal growth factor receptor of the intestinal enterocyte. Localization to laterobasal but not brush border membrane. J Biol Chem 264:1735-1741, 1989

    Article  CAS  PubMed  Google Scholar 

  17. Thompson JF, van den Berg M, Stokkers PC: Developmental regulation of epidermal growth factor receptor kinase in rat intestine. Gastroenterology 107:1278-1287, 1994

    Article  CAS  PubMed  Google Scholar 

  18. Tarnawski A, Stachura J, Durbin T, Sarfeh IJ, Gergely H: Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats. Gastroenterology 102:695-698, 1992

    Article  CAS  PubMed  Google Scholar 

  19. Tarnawski A, Lu SY, Stachura J, Sarfeh IJ: Adaptation of gastric mucosa to chronic alcohol administration is associated with increased mucosal expression of growth factors and their receptor. Scand J Gastroenterol Suppl 193:59-63, 1992

    Article  CAS  PubMed  Google Scholar 

  20. Skinner KA, Tepperman BL: Influence of desalivation on acid secretory output and gastric mucosal integrity in the rat. Gastroenterology 81:335-339, 1981

    Article  CAS  PubMed  Google Scholar 

  21. Bamba T, Tsujikawa T, Hosoda S: Effect of epidermal growth factor by different routes of administration on the small intestinal mucosa of rats fed elemental diet. Gastroenterol Jpn 28:511-517, 1993

    Article  CAS  PubMed  Google Scholar 

  22. Hardin JA, Wong JK, Cheeseman CI, Gall DG: Effect of luminal epidermal growth factor on enterocyte glucose and proline transport. Am J Physiol 271:G509-G515, 1996

    CAS  PubMed  Google Scholar 

  23. Marchbank T, Goodlad RA, Lee CY, Playford RJ: Luminal epidermal growth factor is trophic to the small intestine of parenterally fed rats. Clin Sci 89:117-120, 1995

    Article  CAS  Google Scholar 

  24. O'Loughlin E, Winter M, Shun A, Hardin JA, Gall DG: Structural and functional adaptation following jejunal resection in rabbits: Effect of epidermal growth factor [see comments]. Gastroenterology 107:87-93, 1994

    Article  CAS  PubMed  Google Scholar 

  25. Ulshen MH, Lyn-Cook LE, Raasch RH: Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology 91:1134-1140, 1986

    Article  CAS  PubMed  Google Scholar 

  26. Sarac TP, Seydel AS, Ryan CK, Bessey PQ, Miller JH, Souba WW, Sax HC: Sequential alterations in gut mucosal amino acid and glucose transport after 70-percent small bowel resection. Surgery 120:503-508, 1996

    Article  CAS  PubMed  Google Scholar 

  27. Stevens BR, Kaunitz JD, Wright EM: Intestinal transport of amino acids and sugars: advances using membrane vesicles. Annu Rev Physiol 46:417-433, 1984

    Article  CAS  PubMed  Google Scholar 

  28. Pacha J, Teisinger J, Popp M, Capek K: Na,K-ATPase and the development of Na1 transport in rat distal colon. J Mem Biol 120:201-210, 1991

    Article  CAS  Google Scholar 

  29. Mircheff AK, Wright EM: Analytical isolation of plasma membranes of intestinal epithelial cells: identification of Na, K-ATPase-rich membranes and the distribution of enzyme activities. J Mem Biol 28:309-333, 1976

    Article  CAS  Google Scholar 

  30. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275, 1951

    Article  CAS  PubMed  Google Scholar 

  31. Warner BW, Vanderkolk WE, Can G, Helmrath MA, Shin CE, Erwin CR: Epidermal growth factor receptor expression following small bowel resection. J Sur Res 70:171-177, 1997

    Article  CAS  Google Scholar 

  32. Helmrath MA, Shin CE, Erwin CR, Warner BW: Epidermal growth factor upregulates the expression of its own intestinal receptor after small bowel resection. J Pediatr Sur 33:229-233, 1998

    Article  CAS  Google Scholar 

  33. Helmrath MA, Shin CE, Erwin CR, Warner BW: Intestinal adaptation is enhanced by epidermal growth factor independent of increased ileal epidermal growth factor receptor expression. J Pediatr Sur 33:980-984, 1998

    Article  CAS  Google Scholar 

  34. Sturm A, Layer P, Goebell H, Dignass AU: Short-bowel syndrome: An update on the therapeutic approach. Scand J Gastroenterol 32:289-296, 1997

    Article  CAS  PubMed  Google Scholar 

  35. Kudlow JE, Cheung CY, Bjorge JD: Epidermal growth factor stimulates the synthesis of its own receptor in a human breast cancer cell line. J Biol Chem 261:4134-4138, 1986

    Article  CAS  PubMed  Google Scholar 

  36. Wilson PD: Epithelial cell polarity and disease. Am J Physiol 272:F434-F442, 1997

    CAS  PubMed  Google Scholar 

  37. Gesualdo L, Di Paolo S, Calabro A, Milani S, Maiorano E, Ranieri E, Pannarale G, Schena FP: Expression of epidermal growth factor and its receptor in normal and diseased human kidney: An immunohistochemical and in situ hybridization study. Kid Inter 49:656-665, 1996

    Article  CAS  Google Scholar 

  38. Miettinen PJ: Transforming growth factor-alpha and epidermal growth factor expression in human fetal gastrointestinal tract. Pediatr Res 33:481-486, 1993

    Article  CAS  PubMed  Google Scholar 

  39. Hormi K, Lehy T: Developmental expression of transforming growth factor-alpha and epidermal growth factor receptor proteins in the human pancreas and digestive tract. Cell Tiss Res 278:439-450, 1994

    Article  CAS  Google Scholar 

  40. Kelly D, McFadyen M, King TP, Morgan PJ: Characterization and autoradiographic localization of the epidermal growth factor receptor in the jejunum of neonatal and weaned pigs. Reprod Fertil Dev 4:183-191, 1992

    Article  CAS  PubMed  Google Scholar 

  41. Menard D, Pothier P: Radioautographic localization of epidermal growth factor receptors in human fetal gut. Gastroenterology 101:640-649, 1991

    Article  CAS  PubMed  Google Scholar 

  42. Thompson JF, Lamprey RM, Stokkers PC: Orogastric EGF enhances c-neu and EGF receptor phosphorylation in suckling rat jejunum in vivo. Am J Physiol 265:G63-G72, 1993

    CAS  PubMed  Google Scholar 

  43. Chaet MS, Arya G, Ziegler MM, Warner BW: Epidermal growth factor enhances intestinal adaptation after massive small bowel resection. J Pediatr Sur 29:1035-1038; discussion 1038-1039, 1994

    Article  CAS  Google Scholar 

  44. Sacks AI, Warwick GJ, Barnard JA: Early proliferative events following intestinal resection in the rat. J Pediatr Gastroenterol Nutr 21:158-164, 1995

    Article  CAS  PubMed  Google Scholar 

  45. Bishop WP, Wen JT: Regulation of Caco-2 cell proliferation by basolateral membrane epidermal growth factor receptors. Am J Physiol 267:G892-G900, 1994

    CAS  PubMed  Google Scholar 

  46. Donowitz M, Montgomery JL, Walker MS, Cohen ME: Brush-border tyrosine phosphorylation stimulates ileal neutral NaCl absorption and brush-border Na(1)-H1 exchange. Am J Physiol 266:G647-G656, 1994

    CAS  PubMed  Google Scholar 

  47. Khurana S, Nath SK, Levine SA, Bowser JM, Tse CM, Cohen ME, Donowitz M: Brush border phosphatidylinositol 3-kinase mediates epidermal growth factor stimulation of intestinal NaCl absorption and Na1/H1 exchange. J Biol Chem 271:9919-9927, 1996

    Article  CAS  PubMed  Google Scholar 

  48. Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tsushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y, Kadowaki T: Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to map kinase activation and gene expression. Endocrine J 45:S27-S31, 1998

    Article  CAS  Google Scholar 

  49. Thompson JF: Specific receptors for epidermal growth factor in rat intestinal microvillus membranes. Am J Physiol 254:G429-G435, 1988

    CAS  PubMed  Google Scholar 

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Avissar, N.E., Wang, H.T., Miller, Jn.H. et al. Epidermal Growth Factor Receptor Is Increased in Rabbit Intestinal Brush Border Membrane After Small Bowel Resection. Dig Dis Sci 45, 1145–1152 (2000). https://doi.org/10.1023/A:1005597918552

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