Top

Published in:

01-04-2009 | Original Article

Apoptosis of interstitial cells of Cajal, smooth muscle cells, and enteric neurons induced by intestinal ischemia and reperfusion injury in adult guinea pigs

Authors: Feng Mei, Sheng Guo, Yang-tao He, Jiang Zhu, De-shan Zhou, Jian-qin Niu, Han-zhi Wang, Yan-ping Tian

Published in: Virchows Archiv | Issue 4/2009

Abstract

This study aimed at evaluating whether apoptosis of interstitial cells of Cajal (ICC), smooth muscle cells (SMC), and enteric neurons was involved in a guinea pig model of intestinal ischemia and reperfusion injury. The small intestinal segments were resected at either 6 (I₆₀/R_6h) and 12 h (I₆₀/R_12h) or 7 (I₆₀/R_7d) to 14 (I₆₀/R_14d) days after 60 min intestinal ischemia in the adult guinea pigs and studied by immunohistochemistry with anti-Kit, 5-bromo-2′-deoxyuridine (BrdU), α-smooth muscle actin, vimentin, and β-tublin III antibodies. Also, apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. In the I₆₀/R_12h injury, there was a ∼50% decrease of Kit+ cells in cell numbers at the level of myenteric plexus and a number of Kit-/vimentin-positive cells were labeled by TUNEL. Also, a few SMC and enteric neurons were TUNEL positive. The Kit+ ICC recovered to normal and a number of Kit-/BrdU-double-positive cells were observed in the I₆₀/R_14d group. Our results indicated that the intestinal I/R injury could lead to apoptosis of ICC, SMC, and enteric neurons which may contribute to the gastrointestinal motility disorders, and proliferation was involved in the recovery of ICC.

Available only for authorised users

Hierholzer C, Kalff JC, Audolfsson G (1999) Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury. Transplantation 68:1244–1254PubMedCrossRef

Shimojima N, Nakaki T, Morikawa Y (2006) Interstitial cells of Cajal in dysmotility in intestinal ischemia and reperfusion injury in rats. J Surg Res 135:255–261PubMedCrossRef

Udassin R, Eimerl D, Schiffman J (1995) Postischemic intestinal motility in rat is inversely correlated to length of ischemia. An in vivo animal model. Dig Dis Sci 40:1035–1038PubMedCrossRef

Hassoun HT, Weisbrodt NW, Mercer DW (2001) Inducible nitric oxide synthase mediates gut ischemia/reperfusion-induced ileus only after severe insults. J Surg Res 97:150–154PubMedCrossRef

Hebra A, Hong J, McGowan KL (1994) Bacterial translocation in mesenteric ischemia–reperfusion injury: is dysfunctional motility the link. J Pediatr Surg 29:280–285PubMedCrossRef

Ballabeni V, Barocelli E, Bertoni S (2002) Alterations of intestinal motor responsiveness in a model of mild mesenteric ischemia/reperfusion in rats. Life Sci 71:2025–2035PubMedCrossRef

Ward SM, Sanders KM (2001) Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol 281:G602–G611PubMed

Rumessen JJ, Thuneberg L (1996) Pacemaker cells in the gastrointestinal tract: interstitial cells of Cajal. Scand J Gastroenterol Suppl 216:82–94PubMedCrossRef

Huizinga JD, Berezin I, Chorneyko K (1998) Interstitial cells of Cajal: pacemaker cells. Am J Pathol 153:2008–2011PubMed

10.

Thomsen L, Robinson TL, Lee JC (1998) Interstitial cells of Cajal generate a rhythmic pacemaker current. Nat Med 4:848–851PubMedCrossRef

11.

Huizinga JD, Thuneberg L, Kluppel M (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349PubMedCrossRef

12.

Ward SM, McLaren GJ, Sanders KM (2006) Interstitial cells of Cajal in the deep muscular plexus mediate enteric motor neurotransmission in the mouse small intestine. J Physiol 573:147–159PubMedCrossRef

13.

Rumessen JJ, Mikkelsen HB, Thuneberg L (1992) Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine. Gastroenterol 102:56–68

14.

Zhou DS, Komuro T (1992) Interstitial cells associated with the deep muscular plexus of the guinea-pig small intestine, with special reference to the interstitial cells of Cajal. Cell Tissue Res 268:205–216PubMedCrossRef

15.

Ward SM, Burns AJ, Torihashi S (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 480:91–97PubMed

16.

Kluppel M, Huizinga JD, Malysz J (1998) Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Dev Dyn 211:60–71PubMedCrossRef

17.

Beckett EA, Ro S, Bayguinov Y (2007) Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract. Dev Dyn 236:60–72PubMedCrossRef

18.

Yanagida H, Yanase H, Sanders KM (2004) Intestinal surgical resection disrupts electrical rhythmicity, neural responses, and interstitial cell networks. Gastroenterol 127:1748–1759CrossRef

19.

Chang IY, Glasgow NJ, Takayama I (2001) Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction. J Physiol 536:555–568PubMedCrossRef

20.

Ekblad E, Sjuve R, Arner A (1998) Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum. Gut 42:836–844PubMedCrossRef

21.

Nakajima H, Mizuta N, Fujiwara I (2008) Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia–reperfusion rat liver. Apoptosis 13:1013–1021PubMedCrossRef

22.

Nogae S, Miyazaki M, Kobayashi N (1998) Induction of apoptosis in ischemia–reperfusion model of mouse kidney: possible involvement of Fas. J Am Soc Nephrol 9:620–631PubMed

23.

Luo CC, Shih HH, Chiu CH (2004) Reduced apoptosis in newborn compared to adult rat intestine after ischemia–reperfusion injury. Biol Neonate 85:90–93PubMedCrossRef

24.

Stammberger U, Gaspert A, Hillinger S (2000) Apoptosis induced by ischemia and reperfusion in experimental lung transplantation. Ann Thorac Surg 69:1532–1536PubMedCrossRef

25.

Mei F, Yu B, Ma H (2006) Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs. Virchows Arch 449:348–357PubMedCrossRef

26.

Komuro T, Zhou DS (1996) Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine. J Auton Nerv Syst 61:169–174PubMedCrossRef

27.

Torihashi S, Nishi K, Tokutomi Y (1999) Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype. Gastroenterol 117:140–148CrossRef

28.

Yoshida H, Zhang JJ, Chao L (2000) Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion. Hypertens 35:25–31

29.

Mei F, Zhu J, Guo S (2009) An age-dependent proliferation is involved in the postnatal development of interstitial cells of Cajal in the small intestine of mice. Histochem Cell Biol 131:43–53PubMedCrossRef

30.

Nakahara M, Isozaki K, Vanderwinden JM (2002) Dose-dependent and time-limited proliferation of cultured murine interstitial cells of Cajal in response to stem cell factor. Life Sci 70:2367–2376PubMedCrossRef

31.

Lorincz A, Redelman D, Horvath VJ (2008) Progenitors of interstitial cells of Cajal in the postnatal murine stomach. Gastroenterol 134:1083–1093CrossRef

Title: Apoptosis of interstitial cells of Cajal, smooth muscle cells, and enteric neurons induced by intestinal ischemia and reperfusion injury in adult guinea pigs
Authors: Feng Mei
Sheng Guo
Yang-tao He
Jiang Zhu
De-shan Zhou
Jian-qin Niu
Han-zhi Wang
Yan-ping Tian
Publication date: 01-04-2009
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 4/2009
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-009-0739-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Apoptosis of interstitial cells of Cajal, smooth muscle cells, and enteric neurons induced by intestinal ischemia and reperfusion injury in adult guinea pigs

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2009

The impact of microRNAs on colorectal cancer

Disturbance of circadian gene expression in breast cancer

Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity

Comparison of cyclooxygenase-2 and CD44 mRNA expression in colorectal cancer and its relevance for prognosis

A European network for virtual microscopy—design, implementation and evaluation of performance

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung