Enterocyte Response to Ischemia Is Dependent on Differentiation State

Hinnebusch, Brian F.; Ma, Qing; Henderson, J. Welles; Siddique, Aleem; Archer, Sonia Y.; Hodin, Richard A.
May 2002
Journal of Gastrointestinal Surgery;May2002, Vol. 6 Issue 3, p403
Academic Journal
journal article
Enterocytes at the tips of microvilli are more sensitive to an ischemic insult than those cells residing in the crypts, an effect thought to be due to a relative lack of collateral flow. We speculated that this increased cellular sensitivity to ischemia might be an intrinsic feature of the cells related to their differentiated phenotype. To test this hypothesis, enterocyte response to ischemia was determined using both in vivo and in vitro models. For the in vivo studies, male Sprague-Dawley rats underwent laparotomy, and small intestinal ischemia was induced by clamping the superior mesenteric artery for 30 or 60 minutes, after which reperfusion was allowed for various time points up to 4 days. Injury was assessed histologically, as well as with Northern blots, probing for the enterocyte differentiation markers intestinal alkaline phosphatase and lactase, as well as the gut-epithelial marker villin. Mucosal changes consistent with ischemia/reperfusion injury were evident—that is, a rapid inflammatory response followed by progressive villus cell loss beginning at the tips and progressing to the crypts, depending on the degree of insult, with an eventual return to normal microanatomy. Intestinal alkaline phosphatase and lactase were lost immediately after ischemia and returned with reperfusion, confirming that the differentiated cells are particularly sensitive to ischemic injury. The in vitro studies employed two separate models of enterocyte differentiation: sodium butyrate–treated HT-29 cells and Caco-2 cells maintained for 7 days after confluence. In both models, undifferentiated and differentiated cells were subjected to treatment with 2-deoxyglucose and oligomycin-A (in vitro model of ischemia) and apoptosis was assessed by fluorescence-activated cell sorting analysis. Differentiation of both cell lines resulted in a significantly greater apoptotic response to ischemia compared to undifferentiated cells exposed to an identical insult. We conclude that differentiated enterocytes may be inherently more sensitive to ischemia-induced injury than their undifferentiated counterparts. These findings call into question the popularly held belief that villus tip cells are more susceptible to ischemia because of their location relative to the microvascular anatomy. ( J Gastrointest Surg 2002;6:403–409.)


Related Articles

  • Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. Luedde, Tom; Assrnus, Ulnke; Wüstefeld, Torsten; Vilsendori, Andreas Meyer Zu; Roskams, Tania; Schmidt-supprian, Mark; Rajewsky, Klaus; Brenner, DavidA.; Manns, Michael P.; Pasparakis, Manolis; Trautwein, Christian; Assmus, Ulrike; Wüstefeld, Torsten; Meyer zu Vilsendorf, Andreas; Brenner, David A // Journal of Clinical Investigation;Apr2005, Vol. 115 Issue 4, p849 

    The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved in the activation of NF-kappaB by various stimuli. IKK2 or NEMO constitutive knockout mice die during embryogenesis as a result of massive...

  • Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis. Akilesh, Shreeram; Suleiman, Hani; Yu, Haiyang; Stander, M. Christine; Lavin, Peter; Rasheed, Gbadegesin; Antignac, Corinne; Pollak, Martin; Kopp, Jeffrey B.; Winn, Michelle P.; Shaw, Andrey S.; Gbadegesin, Rasheed // Journal of Clinical Investigation;Oct2011, Vol. 121 Issue 10, p4127 

    The specialized epithelial cell of the kidney, the podocyte, has a complex actin-based cytoskeleton. Dynamic regulation of this cytoskeleton is required for efficient barrier function of the kidney. Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because...

  • Nutritional supplementation with transforming growth factor-beta inhibits intestinal adaptation after massive small bowel resection in a rat. Sukhotnik, Igor; Mogilner, Jorge; Ben Lulu, Shani; Bashenko, Yulia; Shaoul, Ron; Chemodanov, Elena; Coran, Arnold; Mogilner, Jorge G; Coran, Arnold G // Pediatric Surgery International;Feb2011, Vol. 27 Issue 2, p211 

    Introduction: Transforming growth factor beta (TGF-β) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-β2-enriched polymeric...

  • The renal papilla is a niche for adult kidney stem cells. Oliver, Juan A; Maarouf, Omar; Cheema, Faisal H; Martens, Timothy P; Al-Awqati, Qais // Journal of Clinical Investigation;Sep2004, Vol. 114 Issue 5, p795 

    Many adult organs contain stem cells, which are pluripotent and are involved in organ maintenance and repair after injury. In situ, these cells often have a low cycling rate and locate in specialized regions (niches). To detect such cells in the kidney, we administered a pulse of the nucleotide...

  • Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. Ghosh, Goutam; Subramanian, Indira V.; Adhikari, Neeta; Xiaoxiao Zhang; Joshi, Hemant P.; Basi, David; Chandrashekhar, Y. S.; Hall, Jennifer L.; Roy, Sabita; Yan Zeng; Ramakrishnan, Sundaram; Zhang, Xiaoxiao; Zeng, Yan // Journal of Clinical Investigation;Nov2010, Vol. 120 Issue 11, p4141 

    Adaptive changes to oxygen availability are critical for cell survival and tissue homeostasis. Prolonged oxygen deprivation due to reduced blood flow to cardiac or peripheral tissues can lead to myocardial infarction and peripheral vascular disease, respectively. Mammalian cells respond to...

  • Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. Hartleben, Björn; Gödel, Markus; Meyer-Schwesinger, Catherine; Shuya Liu; Ulrich, Theresa; Köbler, Sven; Wiech, Thorsten; Grahammer, Florian; Arnold, Sebastian J.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Pavenstädt, Hermann; Kerjaschki, Dontscho; Mizushima, Noboru; Shaw, Andrey S.; Walz, Gerd; Huber, Tobias B.; Hartleben, Björn; Gödel, Markus; Liu, Shuya // Journal of Clinical Investigation;Apr2010, Vol. 120 Issue 4, p1084 

    Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been...

  • Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion. Bamboat, Zubin M.; Ocuin, Lee M.; Balachandran, Vinod P.; Obaid, Hebroon; Plitas, George; DeMatteo, Ronald P. // Journal of Clinical Investigation;Feb2010, Vol. 120 Issue 2, p559 

    TLRs are recognized as promoters of tissue damage, even in the absence of pathogens. TLR binding to damage-associated molecular patterns (DAMPs) released by injured host cells unleashes an inflammatory cascade that amplifies tissue destruction. However, whether TLRs possess the reciprocal...

  • Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. Gallagher, Katherine A.; Zhao-Jun Liu; Min Xiao; Haiying Chen; Goldstein, Lee J.; Buerk, Donald G.; Nedeau, April; Thom, Stephen R.; Velazquez, Omaida C.; Liu, Zhao-Jun; Xiao, Min; Chen, Haiying // Journal of Clinical Investigation;May2007, Vol. 117 Issue 5, p1249 

    Endothelial progenitor cells (EPCs) are essential in vasculogenesis and wound healing, but their circulating and wound level numbers are decreased in diabetes. This study aimed to determine mechanisms responsible for the diabetic defect in circulating and wound EPCs. Since mobilization of BM...

  • Pancreatic Elastase Induces Liver Injury by Activating Cytokine Production Within Kupffer Cells via Nuclear Factor-Kappa B Murr, Michel M.; Yang, Jun; Fier, Adam; Kaylor, Pam; Mastorides, Stephen; Norman, James G. // Journal of Gastrointestinal Surgery;May2002, Vol. 6 Issue 3, p474 

    Liver injury is a manifestation of the systemic inflammatory response during acute pancreatitis. We have demonstrated that elastase induces macrophage tumor necrosis factor (TNF) production in distant organs, thus mimicking pancreatitis-associated organ injury. The aim of this study was to...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics