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Article: Rap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation

TitleRap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation
Authors
Issue Date2018
PublisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2018, v. 9 n. 3, p. 386 How to Cite?
AbstractImmunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. Our previous studies showed that activation of nuclear factor-kappa B (NF-κB) regulates cytokine/growth factor secretion by MSCs. This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the immunomodulatory potency of MSCs in acute allograft rejection of heart transplantation. The immunosuppressive potency of wild-type MSCs (WT-MSCs) or Rap1-deficient MSCs (Rap1-/--MSCs) was examined in mice with acute allograft rejection following heart transplantation. With a combination of immunosuppressant rapamycin at a dose of 1 mg/kg/d, WT-MSCs notably prolonged the survival of the transplanted heart compared with Rap1-/--MSCs. Rap1-/--MSCs displayed a marked insensitivity to inhibit the mixed lymphocyte reaction (MLR) due to impaired cytokine production and a significantly reduced activity of NF-κB signaling in vitro. Finally, transplantation of encapsulated WT-MSCs greatly prolonged the survival of the heart allograft compared with encapsulated Rap1-/--MSCs. Our results indicate that Rap1 is essential to maintain the immunomodulatory function of MSCs. Deletion of Rap1 results in impaired immunomodulatory function of MSCs.
Persistent Identifierhttp://hdl.handle.net/10722/251860
ISSN
2017 Impact Factor: 5.638
2015 SCImago Journal Rankings: 2.484
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDing, Y-
dc.contributor.authorLiang, X-
dc.contributor.authorZhang, Y-
dc.contributor.authorYi, L-
dc.contributor.authorShum, HC-
dc.contributor.authorChen, Q-
dc.contributor.authorChan, BP-
dc.contributor.authorFan, H-
dc.contributor.authorLiu, Z-
dc.contributor.authorTergaonkar, V-
dc.contributor.authorQi, Z-
dc.contributor.authorTse, HF-
dc.contributor.authorLian, Q-
dc.date.accessioned2018-03-21T07:21:30Z-
dc.date.available2018-03-21T07:21:30Z-
dc.date.issued2018-
dc.identifier.citationCell Death & Disease, 2018, v. 9 n. 3, p. 386-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/251860-
dc.description.abstractImmunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. Our previous studies showed that activation of nuclear factor-kappa B (NF-κB) regulates cytokine/growth factor secretion by MSCs. This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the immunomodulatory potency of MSCs in acute allograft rejection of heart transplantation. The immunosuppressive potency of wild-type MSCs (WT-MSCs) or Rap1-deficient MSCs (Rap1-/--MSCs) was examined in mice with acute allograft rejection following heart transplantation. With a combination of immunosuppressant rapamycin at a dose of 1 mg/kg/d, WT-MSCs notably prolonged the survival of the transplanted heart compared with Rap1-/--MSCs. Rap1-/--MSCs displayed a marked insensitivity to inhibit the mixed lymphocyte reaction (MLR) due to impaired cytokine production and a significantly reduced activity of NF-κB signaling in vitro. Finally, transplantation of encapsulated WT-MSCs greatly prolonged the survival of the heart allograft compared with encapsulated Rap1-/--MSCs. Our results indicate that Rap1 is essential to maintain the immunomodulatory function of MSCs. Deletion of Rap1 results in impaired immunomodulatory function of MSCs.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleRap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation-
dc.typeArticle-
dc.identifier.emailShum, HC: ashum@hku.hk-
dc.identifier.emailChan, BP: bpchan@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityShum, HC=rp01439-
dc.identifier.authorityChan, BP=rp00087-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-018-0414-3-
dc.identifier.pmid29515165-
dc.identifier.pmcidPMC5842217-
dc.identifier.hkuros290225-
dc.identifier.volume9-
dc.identifier.issue3-
dc.identifier.spage386-
dc.identifier.epage386-
dc.identifier.isiWOS:000427426100016-
dc.publisher.placeUnited Kingdom-

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