TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology.
Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3150355?pdf=render |
| _version_ | 1819052229438472192 |
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| author | Nancy Vargas Silvia Álvarez-Cubela Jaime A Giraldo Margarita Nieto Nicholas M Fort Sirlene Cechin Enrique García Pedro Espino-Grosso Christopher A Fraker Camillo Ricordi Luca Inverardi Ricardo L Pastori Juan Domínguez-Bendala |
| author_facet | Nancy Vargas Silvia Álvarez-Cubela Jaime A Giraldo Margarita Nieto Nicholas M Fort Sirlene Cechin Enrique García Pedro Espino-Grosso Christopher A Fraker Camillo Ricordi Luca Inverardi Ricardo L Pastori Juan Domínguez-Bendala |
| author_sort | Nancy Vargas |
| collection | DOAJ |
| description | Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar cells into insulin-producing beta cells. These experiments set the stage for the development of new strategies to address the impairment of glycemic control in diabetic patients. However, the clinical applicability of reprogramming in this context is deemed to be poor due to the need to use viral vehicles for the delivery of the above factors. Here we describe a recombinant transducible version of the MafA protein (TAT-MafA) that penetrates across cell membranes with an efficiency of 100% and binds to the insulin promoter in vitro. When injected in utero into living mouse embryos, TAT-MafA significantly up-regulates target genes and induces enhanced insulin production as well as cytoarchitectural changes consistent with faster islet maturation. As the latest addition to our armamentarium of transducible proteins (which already includes Pdx1 and Ngn3), the purification and characterization of a functional TAT-MafA protein opens the door to prospective therapeutic uses that circumvent the use of viral delivery. To our knowledge, this is also the first report on the use of protein transduction in utero. |
| first_indexed | 2024-12-21T12:16:31Z |
| format | Article |
| id | doaj.art-c77a0084b2e34d4f9d9c6b647d41f407 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T12:16:31Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c77a0084b2e34d4f9d9c6b647d41f4072022-12-21T19:04:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2236410.1371/journal.pone.0022364TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology.Nancy VargasSilvia Álvarez-CubelaJaime A GiraldoMargarita NietoNicholas M FortSirlene CechinEnrique GarcíaPedro Espino-GrossoChristopher A FrakerCamillo RicordiLuca InverardiRicardo L PastoriJuan Domínguez-BendalaAlongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar cells into insulin-producing beta cells. These experiments set the stage for the development of new strategies to address the impairment of glycemic control in diabetic patients. However, the clinical applicability of reprogramming in this context is deemed to be poor due to the need to use viral vehicles for the delivery of the above factors. Here we describe a recombinant transducible version of the MafA protein (TAT-MafA) that penetrates across cell membranes with an efficiency of 100% and binds to the insulin promoter in vitro. When injected in utero into living mouse embryos, TAT-MafA significantly up-regulates target genes and induces enhanced insulin production as well as cytoarchitectural changes consistent with faster islet maturation. As the latest addition to our armamentarium of transducible proteins (which already includes Pdx1 and Ngn3), the purification and characterization of a functional TAT-MafA protein opens the door to prospective therapeutic uses that circumvent the use of viral delivery. To our knowledge, this is also the first report on the use of protein transduction in utero.http://europepmc.org/articles/PMC3150355?pdf=render |
| spellingShingle | Nancy Vargas Silvia Álvarez-Cubela Jaime A Giraldo Margarita Nieto Nicholas M Fort Sirlene Cechin Enrique García Pedro Espino-Grosso Christopher A Fraker Camillo Ricordi Luca Inverardi Ricardo L Pastori Juan Domínguez-Bendala TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. PLoS ONE |
| title | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| title_full | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| title_fullStr | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| title_full_unstemmed | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| title_short | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| title_sort | tat mediated transduction of mafa protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology |
| url | http://europepmc.org/articles/PMC3150355?pdf=render |
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