Dissertation > Excellent graduate degree dissertation topics show

KGF Improves Intestinal Structure and Function in a Mouse Model of Intestinal Ischemia/Reperfusion: Mechanism Involved in the Up-regulation of Epithelial Derived IL-7Expression

Author: CaiZuoJiao
Tutor: YangZuo
School: Third Military Medical University
Course: Surgery
Keywords: Keratinocyte growth factor (KGF) Interleukin-7(IL-7) ischemia/reperfusion (I/R) mouse intestinal epithelial cells intestinal barrier function signaltransducers and activators of transcription1(STAT1) interferon regulatory factor1(IRF-1)and interferon regulatory factor2(IRF-2)
CLC: R656.7
Type: PhD thesis
Year: 2012
Downloads: 60
Quote: 0
Read: Download Dissertation

Abstract


Background:Intestinal ischemia/reperfusion (I/R) induces the desquamation of the intestinalepithelium, increases the intestinal permeability, and in patients often causes fatal conditionsincluding sepsis and multiple organ failure. Keratinocyte growth factor (KGF) increasesintestinal growth, although little is known about the effect of KGF on intestinal function afterintestinal I/R. Epithelial cell (EC) derived Interleukin-7(IL-7) plays a crucial role in controlof neighbouring intraepithelial lymphocytes (IEL) development and homeostasis, and IELderived KGF promotes intestinal epithelial growth, which was regulated by EC-derived IL-7.These two factors are both important involved in the regulation of gastrointestinal cell growthand function. Base on this, we hypothesized that KGF administration would improve theintestinal function in a mouse model of acute intestinal I/R, we also hypothesized that there isa crosstalk between IELs and ECs through IEL derived KGF and EC derived IL-7, and KGFcould regulate the EC-derived IL-7expression. Furthermore, to investigate the mechanisminvolved in this regulation of IL-7expression by KGF.Methods:Firstly, adult C57BL/6J mice undergoing intestinal I/R injury were treated withrecombinant KGF. Mice were killed after surgery, and the small bowel was harvested forhistology, wet weight, RNA and protein content analysis. ECs proliferation was detected byimmunohistochemistry for PCNA, and apoptosis was determined by TUNEL staining. Theexpressions of Claudin-1and ZO-1were detected by immunohistochemistry. Epithelialbarrier function was assessed with transepithelial resistance (TER).Secondly, histological evaluation was performed in small intestine tissues of patients with intestinal obstruction and IL-7expression was detected by immunofluorescence.Intestinal epithelial cells (LoVo cells) and adult C57BL/6J mice were treated withrecombinant KGF. KGF, KGF receptor (KGFR) and IL-7expressions were measured withwestern blot and immunofluorescence analysis.Thirdly, LoVo cells and adult C57BL/6J mice were treated with KGF. Changes of IL-7expression following KGFR blockade or KGFR RNA interference with KGF treatment andexpression of P-Tyr-STAT1, STAT1, and IL-7by inhibiting STAT1and alterations ofexpression of IRF-1, IRF-2and IL-7following IRF-1and IRF-2RNA interference with KGFtreatment were measured with western blot. In addition, IRF-1, IRF-2expression weredetected by immunofluorescence in vitro and immunohistochemistry analysis in vivo.Results:1. KGF treatment significantly increased the intestinal mucosal wet weight, contents ofintestinal mucosal protein and RNA, villus height, crypt depth and crypt cell proliferation,while KGF administration resulted in the decrease of EC apoptosis in a mouse model ofintestinal I/R.2. KGF also stimulated the recovery of mucosal structures and attenuated the disrupteddistribution of TJ proteins in a mouse model of intestinal I/R.3. Moreover, KGF administration attenuated the intestinal I/R-induced decrease in TERand maintained the intestinal barrier function.4. KGF expression in the intestinal mucosa significantly decreased while IL-7expressionincreased early after acute intestinal I/R in a mouse model.5. KGF treatment significantly increased the EC derived IL-7expression both in vitroand in vivo studies. In addition, KGF administration significantly attenuated the decreasing ofIL-7expression caused by acute intestinal I/R.6. IL-7expression was decreased after KGFR blockade or KGFR expression wassilenced by using interfering RNA in LoVo cells, even following KGF treatment.7. KGF treatment led to increased levels of P-Tyr-STAT1, RPM and AG490bothblocked P-Tyr-STAT1and IL-7expression in LoVo cells.8. IRF-1and IRF-2expressions in vivo and in vitro studies are also up-regulated by KGF,and IL-7expression was decreased after IRF-1or IRF-2expression was silenced by usinginterfering RNA following KGF treatment, respectively. Conclusion:KGF administration improves the intestinal structure and intestinal barrier function in amouse model of intestinal I/R. KGF could up-regulate the EC derived IL-7expression both invitro and in vivo through KGFR/STAT1/IRF-1, IRF-2signaling pathway. These findings arethe first report of mechanism that KGFR/STAT1/IRF-1, IRF-2pathway involved in theregulation of IL-7expression by KGF, which suggest that KGF may play an important role inthe regulation of IEL function by regulating IL-7expression.

Related Dissertations

  1. Effects of Isoprocarb Exposure on Differentiation, Migration and Neurite Outgrowth of the Key Cell During Neural Development in Vitro,R329
  2. A Model of Acute Interstitial Pneumonitis by Murine Cytomegalovirus Infection in Mice with Allogenic Skin Transplantation,R-332
  3. The Protective Effect of Rat Myocardial Ischemia/reperfusion Injury Following Bone Marrow Mesenchymal Stem Cell Pretransplantation for 1 Week,R542.22
  4. Therapeutic Effects of TACI-Ig on Systemic Lupus Erythematosus-like Mouse Model Induced by Active Chromatin Isolated from ConA-actived Lymphocytes,R593.241
  5. Effects of Partial Hepatic Ischemia/Reperfusion Injury on Postoperative Cognitive Function in Mice,R614
  6. Effect of Ipriflavone on the New Calcium Channel Expression of Chicken Embryonic Small Intestinal Epithelial Cells in Vitro,S831
  7. Expression and Significance of HIF-1α on the Insulin Resistance during the Injury of Reperfusion of Ischemic Myocardium in Dog Undergoing Cardiopulmonary Bypass,R654.1
  8. Identification of Recombinant Adenovirus Carrying Mouse Estrogen Receptor α in Infected Neurons and Central Nervous System,R363
  9. Effect of Nrf2-ARE Pathway on Isolated Rat Hearts Using Ischemia or Pinacidil Postconditioning,R96
  10. Method of Stored Grain Pest Control in Rural Areas,S379
  11. Protective Effect of Huangqi Injection in Children’s Mechanical Ileus Ischemia-reperfusion Injury,R272
  12. The Effects of Prostaglantiain E1 to the Phenotype and Functional Activity of Macrophage Which in Mouse Uterus,R363
  13. The Exploration of Aldehyde Dehydrogenase 2 in the Cardioprotection of Fasudil,R54
  14. The Influence of Cold Self-bloodcardioplegia to MMP-2 Concentration for Infant with Cardiopulmulnary Bypass,R726.5
  15. The Function and Mechanism of Endoplasmic Reticulum Stress Pre-treatment on the Improvement of Renal Tolerance Toward Ischemia-reperfusion Injury,R692.5
  16. The Relevance Research of Neuroglobin and Caspase-3 in the Hippocampus CA1 Regin in Global Cerebral Ischemia-reperfused Rats,R741
  17. Effects of bFGF on p-Akt (Ser473) and Fractalkine Expression in Cerebral Ischemia/Reperfusion of Rats,R743.3
  18. Age-Related Alteration of NSF Levels in Different Brain Regions and Their Correlations with Spatial Learning Memory in Mice,R741
  19. The Experimental Study of Atorvastatin with Neuroprotective Effects by Inhibiting MMP-9 and Upregulating TIMP-1 Expression in Rat Stroke Model of Focal Cerebral Ischemia/Reperfusion,R743.33
  20. Neuroprotective Mechanism of NBP Preconditioning in Cerebral Ischemia Reperfusion Injury on Sprague-Dawley Rats,R743.33
  21. The Effects of OCT-poloxamer 407 Thermosensitive Gel on Proliferation and Apoptosis of Hca-F Cell and Study on Its Residence Time Within the Solid Tumor in Mice,R735.7

CLC: > Medicine, health > Surgery > Of surgery > Abdominal surgery > Small intestine
© 2012 www.DissertationTopic.Net  Mobile