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- Publisher Website: 10.1038/s41419-018-0414-3
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- PMID: 29515165
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Article: Rap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation
Title | Rap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation |
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Authors | |
Issue Date | 2018 |
Publisher | Nature 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? |
Abstract | Immunomodulatory 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 Identifier | http://hdl.handle.net/10722/251860 |
ISSN | 2023 Impact Factor: 8.1 2023 SCImago Journal Rankings: 2.447 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ding, Y | - |
dc.contributor.author | Liang, X | - |
dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Yi, L | - |
dc.contributor.author | Shum, HC | - |
dc.contributor.author | Chen, Q | - |
dc.contributor.author | Chan, BP | - |
dc.contributor.author | Fan, H | - |
dc.contributor.author | Liu, Z | - |
dc.contributor.author | Tergaonkar, V | - |
dc.contributor.author | Qi, Z | - |
dc.contributor.author | Tse, HF | - |
dc.contributor.author | Lian, Q | - |
dc.date.accessioned | 2018-03-21T07:21:30Z | - |
dc.date.available | 2018-03-21T07:21:30Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Cell Death & Disease, 2018, v. 9 n. 3, p. 386 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | http://hdl.handle.net/10722/251860 | - |
dc.description.abstract | Immunomodulatory 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.language | eng | - |
dc.publisher | Nature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/cddis/index.html | - |
dc.relation.ispartof | Cell Death & Disease | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Rap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation | - |
dc.type | Article | - |
dc.identifier.email | Shum, HC: ashum@hku.hk | - |
dc.identifier.email | Chan, BP: bpchan@hku.hk | - |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | - |
dc.identifier.email | Lian, Q: qzlian@hkucc.hku.hk | - |
dc.identifier.authority | Shum, HC=rp01439 | - |
dc.identifier.authority | Chan, BP=rp00087 | - |
dc.identifier.authority | Tse, HF=rp00428 | - |
dc.identifier.authority | Lian, Q=rp00267 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41419-018-0414-3 | - |
dc.identifier.pmid | 29515165 | - |
dc.identifier.pmcid | PMC5842217 | - |
dc.identifier.scopus | eid_2-s2.0-85048282502 | - |
dc.identifier.hkuros | 290225 | - |
dc.identifier.volume | 9 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 386 | - |
dc.identifier.epage | 386 | - |
dc.identifier.isi | WOS:000427426100016 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 2041-4889 | - |