Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Guan, Yanfang; Worrell, Roger T.; Pritts, Timothy A.; Montrose, Marshall H.

doi:10.1152/ajpgi.90595.2008

Cited by 70 publications

(75 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, our observation that a longer period of SMAO (45 min) followed by 3 h of reperfusion was associated with pronounced intestinal and lung injury and inflammation is consistent with studies demonstrating that the magnitude of apoptosis and severity of mucosal injury is directly proportional to the duration of intestinal ischemic insult (4,37). Furthermore, real-time analysis of acute mucosal events in the villus epithelium demonstrated that although strong intracellular acidification and increased mitochondrial energy production were evident in the jejunum within 5 min of ischemia, the adverse effects of a short period of ischemia (15 min) were reversible upon reperfusion, whereas after a long period of ischemia (40 -50 min), mucosal damage was irreversible upon reperfusion (19). Taken together, these results suggest that the duration and severity of the intestinal ischemic insult are critical determinants of whether HIF-1 plays a gut-protective or deleterious role.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury

Kannan

Colorado

Reino

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

DZ, Semenza GL, Deitch EA, Feinman R. Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury. Am J Physiol Gastrointest Liver Physiol 300: G853-G861, 2011. First published December 23, 2010 doi:10.1152/ajpgi.00459.2010.-Gut injury and loss of normal intestinal barrier function are key elements in the paradigm of gutorigin systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome (MODS). As hypoxiainducible factor (HIF-1) is a critical determinant of the physiological and pathophysiological response to hypoxia and ischemia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Using partially HIF-1␣-deficient mice in an isolated superior mesenteric artery occlusion (SMAO) intestinal ischemia reperfusion (I/R) injury model (45 min SMAO followed by 3 h of reperfusion), we showed a direct relationship between HIF-1 activation and intestinal I/R injury. Specifically, partial HIF-1␣ deficiency attenuated SMAO-induced increases in intestinal permeability, lipid peroxidation, mucosal caspase-3 activity, and IL-1␤ mRNA levels. Furthermore, partial HIF-1␣ deficiency prevented the induction of ileal mucosal inducible nitric oxide synthase (iNOS) protein levels after SMAO and iNOS deficiency ameliorated SMAO-induced villus injury. Resistance to SMAO-induced gut injury was also associated with resistance to lung injury, as reflected by decreased levels of myeloperoxidase, IL-6 and IL-10 in the lungs of HIF-1␣ ϩ/Ϫ mice. In contrast, a short duration of SMAO (15 min) followed by 3 h of reperfusion neither induced mucosal HIF-1␣ protein levels nor caused significant gut and lung injury in wild-type or HIF-1␣ ϩ/Ϫ mice. This study indicates that intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. However, the duration and severity of the gut I/R insult dictate whether HIF-1 plays a gut-protective or deleterious role.inflammation; inducible nitric oxide synthase; mucosal injury MULTIPLE ORGAN DYSFUNCTION syndrome (MODS) is the major cause of morbidity and mortality in critically ill patients. A key paradigm in the development of the systemic inflammatory response syndrome (SIRS) and acute respiratory distress syndrome (ARDS) that culminates in multiple organ dysfunction syndrome (MODS) is loss of intestinal barrier function (10, 12). Intestinal ischemia reperfusion (I/R) injury occurs in different clinical settings, such as trauma, shock, burn, mesenteric artery occlusion, abdominal, cardiac bypass, and thoracic vascular surgery, as well as small intestinal transplantation.Because the gut acts as the "motor" of SIRS, ARDS, and MODS (6) and therapy for the critically ill patient remains largely supportive, studies identifying the underlying pathophysiological factors in the gut that initiate and propagate SIRS, ARDS, and MODS are of critical importance. To date, studies investigating the gut inflammatory/injurious response have primarily fo...

show abstract

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury

Kannan

Colorado

Reino

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Mice (age ϳ12 wk) were surgically prepared for imaging of the exposed small intestinal villi, by modification of previous procedures (12), as summarized below. They were anesthetized by intraperitoneal injection of ketamine hydrochloride (50 mg/kg body wt; Ketaject, Phoenix Scientific, St. Joseph, MO) and thiobutyl barbital (120 mg/kg body wt; Inactin; Sigma Chemical, St. Louis, MO).…”

Section: Animalsmentioning

confidence: 99%

“…Using a transgenic mouse expressing a fusion protein between monomeric red fluorescent protein (mRFP1) and ZO-1 (20), intravital staining (12,16) and immunofluorescence, we have examined the subcellular redistribution of ZO-1 while directly visualizing physiological cell shedding without pharmacological or mechanical stimulation. As a result, we here report for the first time the three-dimensional and temporal dynamics of physiological cell extrusion in relation to epithelial barrier function in the intestine.…”

mentioning

confidence: 99%

Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Guan

Watson

Marchiando

et al. 2011

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

We questioned how tight junctions contribute to intestinal barrier function during the cell shedding that is part of physiological cell renewal. Intravital confocal microscopy studied the jejunal villus epithelium of mice expressing a fluorescent zonula occludens 1 (ZO-1) fusion protein. Vital staining also visualized the cell nucleus (Hoechst staining) or local permeability to luminal constituents (Lucifer Yellow; LY). In a cell fated to be shed, ZO-1 redistributes from the tight junction toward the apical and then basolateral cell region. ZO-1 rearrangement occurs 15 Ϯ 6 min (n ϭ 28) before movement of the cell nucleus from the epithelial layer. During cell extrusion, permeation of luminal LY extends along the lateral intercellular spaces of the shedding cell only as far as the location of ZO-1. Within 3 min after detachment from the epithelial layer, nuclear chromatin condenses. After cell loss, a residual patch of ZO-1 remains in the space previously occupied by the departed cell, and the size of the patch shrinks to 14 Ϯ 2% (n ϭ 15) of the original cell space over 20 min. The duration of cell shedding measured by nucleus movement (14 Ϯ 1 min) is much less than the total duration of ZO-1 redistribution at the same sites (45 Ϯ 2 min). In about 15% of cell shedding cases, neighboring epithelial cells also undergo extrusion with a delay of 5-10 min. With the use of normal mice, ZO-1 immunofluorescent staining of fixed tissue confirmed ZO-1 redistribution and the presence of ZO-1 patches beneath shedding cells. Immunostaining also showed that redistribution of ZO-1 occurred without corresponding mixing of apical and basolateral membrane domains as marked by ezrin or Ecadherin. ZO-1 redistribution is the earliest cellular event yet identified as a herald of physiological cell shedding, and redistribution of tight junction function along the lateral plasma membrane sustains epithelial barrier during cell shedding. jejunum; fluorescent protein; intestinal permeability; intravital microscopy; laser scanning confocal microscopy; multiphoton microscopy

show abstract

“…Intestinal mucosal injury (IMI) is a common clinical complication that may lead to dysfunction of the intestinal barrier. The most common cause of IMI includes acute intestinal obstruction (AIO), especially strangulated intestinal obstruction (STR-IO), followed by chronic intestinal obstruction (2,3), severe trauma (4-6), intestinal ischemia (7)(8)(9) and acute pancreatitis (10)(11)(12). A cascade of intestinal events such as overproduction of intestinal cytokines (13) and increased intestinal permeability (14) and translocation of intestinal bacteria and endotoxins may be initiated in these diseases (15).…”

Section: Introductionmentioning

confidence: 99%

Histidine Decarboxylase Is Identified as a Potential Biomarker of Intestinal Mucosal Injury in Patients with Acute Intestinal Obstruction

Yang

Zhāng

et al. 2011

Mol Med

View full text Add to dashboard Cite

Various biomarkers currently used for the diagnosis of intestinal mucosal injury (IMI) in patients with acute intestinal obstruction have low sensitivity and specificity. In the present study, IMI, as indicated by the impaired expression of tight junction proteins, including zonula occludens-1, occludin and claudin-1, and inflammation were determined in colonic tissues of patients with 45 strangulated intestinal obstruction (STR-IO) and the adjacent "normal" colonic tissues of 35 patients with colon cancers by quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting, immunohistochemistry and histological examination, respectively. Then, two-dimensional fluorescent difference gel electrophoresis coupled with linear trap quadrupole mass spectrometry was used to screen for potential biomarkers of IMI in the serum samples of 10 STR-IO, 10 simple intestinal obstruction (SIM-IO) and 10 normal healthy controls. A total of 35 protein spots were differentially expressed among the serum samples, and six of the proteins were identified as potential biomarkers. Among the six proteins, histidine decarboxylase (HDC) and ceruloplasmin (CP) were elevated significantly in patients with STR-IO, compared with patients with SIM-IO and healthy controls. Thus, HDC and CP were further validated by QRT-PCR, Western blotting, immunohistochemistry and enzyme-linked immunosorbent assay, respectively, in colonic tissues, serum and urine samples. Finally, the receiver operating characteristic curves were used to show the area under the curves of HDC, CP and several established biomarkers, followed by the determination of the appropriate cutoff values and their sensitivities and specificities. It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of IMI in patients with acute intestinal obstruction, although further validation in a larger cohort is required.

show abstract

Intestinal ischemia-reperfusion injury: reversible and irreversible damage imaged in vivo

Cited by 70 publications

References 34 publications

Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury

Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury

Redistribution of the tight junction protein ZO-1 during physiological shedding of mouse intestinal epithelial cells

Histidine Decarboxylase Is Identified as a Potential Biomarker of Intestinal Mucosal Injury in Patients with Acute Intestinal Obstruction

Contact Info

Product

Resources

About