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Article: Inhibition of sonic hedgehog signaling reduces chronic rejection and prolongs allograft survival in a rat orthotopic small bowel transplantation model

TitleInhibition of sonic hedgehog signaling reduces chronic rejection and prolongs allograft survival in a rat orthotopic small bowel transplantation model
Authors
KeywordsChronic rejection
Sonic hedgehog
Vascular endothelial growth factor
Issue Date2007
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com
Citation
Transplantation, 2007, v. 83 n. 10, p. 1351-1357 How to Cite?
AbstractBACKGROUND. Although acute graft rejection can be successfully controlled by immunosuppressive agents, chronic rejection (CR), which is characterized by arteriosclerosis in the donor organ vessels, is a major hurdle to long-term allograft survival. Sonic hedgehog (Shh), a morphogen critical in embryogenesis, also promotes peripheral immunity, which prompted us to investigate if inhibition of Shh signaling could reduce CR and thereby enhance allograft survival. METHODS. In a rat orthotopic small bowel transplantation model, FK506 prevented acute rejection; however, recipients eventually lost their grafts by CR. Anti-Shh antibody or isotype control were administered to animals at day 30 postoperatively. Graft survival, tissue fibrosis, vascular occlusion, and expression of vascular endothelial growth factor (VEGF) were investigated. RESULTS. Immunostaining revealed that Shh and the Hedgehog receptor Patched 1 (Ptc1) are strongly expressed in CR grafts and that Ptc1 expression partially overlapped with that of ED-1, a macrophage marker. In contrast, only minimal expression of Shh and Ptc1 was detected in syngeneic grafts. Grafts survival was significantly prolonged after anti-Shh antibody treatment compared with the immunoglobulin G control (116 vs. 77.5 days). Collagen deposition and vascular occlusion in the mesentery were markedly reduced in recipients of the anti-Shh antibody. Specific transcripts and protein expression for VEGF, which was present mainly in the blood vessels, were reduced. CONCLUSION. In a rat small bowel transplantation model, anti-Shh antibody treatment reduced CR and prolonged graft survival. These beneficial effects of Shh treatment may occur partly by reducing VEGF expression in the blood vessels of the allografts. © 2007 Lippincott Williams & Wilkins, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/83158
ISSN
2015 Impact Factor: 3.69
2015 SCImago Journal Rankings: 1.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLi, Xen_HK
dc.contributor.authorTian, Len_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorDallman, MJen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T08:37:41Z-
dc.date.available2010-09-06T08:37:41Z-
dc.date.issued2007en_HK
dc.identifier.citationTransplantation, 2007, v. 83 n. 10, p. 1351-1357en_HK
dc.identifier.issn0041-1337en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83158-
dc.description.abstractBACKGROUND. Although acute graft rejection can be successfully controlled by immunosuppressive agents, chronic rejection (CR), which is characterized by arteriosclerosis in the donor organ vessels, is a major hurdle to long-term allograft survival. Sonic hedgehog (Shh), a morphogen critical in embryogenesis, also promotes peripheral immunity, which prompted us to investigate if inhibition of Shh signaling could reduce CR and thereby enhance allograft survival. METHODS. In a rat orthotopic small bowel transplantation model, FK506 prevented acute rejection; however, recipients eventually lost their grafts by CR. Anti-Shh antibody or isotype control were administered to animals at day 30 postoperatively. Graft survival, tissue fibrosis, vascular occlusion, and expression of vascular endothelial growth factor (VEGF) were investigated. RESULTS. Immunostaining revealed that Shh and the Hedgehog receptor Patched 1 (Ptc1) are strongly expressed in CR grafts and that Ptc1 expression partially overlapped with that of ED-1, a macrophage marker. In contrast, only minimal expression of Shh and Ptc1 was detected in syngeneic grafts. Grafts survival was significantly prolonged after anti-Shh antibody treatment compared with the immunoglobulin G control (116 vs. 77.5 days). Collagen deposition and vascular occlusion in the mesentery were markedly reduced in recipients of the anti-Shh antibody. Specific transcripts and protein expression for VEGF, which was present mainly in the blood vessels, were reduced. CONCLUSION. In a rat small bowel transplantation model, anti-Shh antibody treatment reduced CR and prolonged graft survival. These beneficial effects of Shh treatment may occur partly by reducing VEGF expression in the blood vessels of the allografts. © 2007 Lippincott Williams & Wilkins, Inc.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.comen_HK
dc.relation.ispartofTransplantationen_HK
dc.rightsTransplantation. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subjectChronic rejectionen_HK
dc.subjectSonic hedgehogen_HK
dc.subjectVascular endothelial growth factoren_HK
dc.titleInhibition of sonic hedgehog signaling reduces chronic rejection and prolongs allograft survival in a rat orthotopic small bowel transplantation modelen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0041-1337&volume=83&issue=10&spage=1351&epage=1357&date=2007&atitle=Inhibition+of+sonic+hedgehog+signaling+reduces+chronic+rejection+and+prolongs+allograft+survival+in+a+rat+orthotopic+small+bowel+transplantation+modelen_HK
dc.identifier.emailChen, Y: ychenc@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp01318en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/01.tp.0000262568.73590.81en_HK
dc.identifier.pmid17519786-
dc.identifier.scopuseid_2-s2.0-34249109356en_HK
dc.identifier.hkuros127446en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34249109356&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume83en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1351en_HK
dc.identifier.epage1357en_HK
dc.identifier.isiWOS:000246792200011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, Y=36463185300en_HK
dc.identifier.scopusauthoridLi, X=15728244800en_HK
dc.identifier.scopusauthoridTian, L=7202296389en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridDallman, MJ=35473592200en_HK
dc.identifier.scopusauthoridLamb, JR=7201524642en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK

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