Cargando…
T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1
T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171881/ https://www.ncbi.nlm.nih.gov/pubmed/30286151 http://dx.doi.org/10.1371/journal.pone.0204775 |
_version_ | 1783360843050647552 |
---|---|
author | Bresin, Antonella Ragone, Gianluca Cristofoletti, Cristina Arcelli, Diego Bassi, Cristian Caprini, Elisabetta Fiorenza, Maria Teresa Helmer Citterich, Mauro Russo, Giandomenico Narducci, Maria Grazia |
author_facet | Bresin, Antonella Ragone, Gianluca Cristofoletti, Cristina Arcelli, Diego Bassi, Cristian Caprini, Elisabetta Fiorenza, Maria Teresa Helmer Citterich, Mauro Russo, Giandomenico Narducci, Maria Grazia |
author_sort | Bresin, Antonella |
collection | PubMed |
description | T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative–differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/- and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs. |
format | Online Article Text |
id | pubmed-6171881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61718812018-10-19 T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 Bresin, Antonella Ragone, Gianluca Cristofoletti, Cristina Arcelli, Diego Bassi, Cristian Caprini, Elisabetta Fiorenza, Maria Teresa Helmer Citterich, Mauro Russo, Giandomenico Narducci, Maria Grazia PLoS One Research Article T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative–differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/- and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs. Public Library of Science 2018-10-04 /pmc/articles/PMC6171881/ /pubmed/30286151 http://dx.doi.org/10.1371/journal.pone.0204775 Text en © 2018 Bresin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bresin, Antonella Ragone, Gianluca Cristofoletti, Cristina Arcelli, Diego Bassi, Cristian Caprini, Elisabetta Fiorenza, Maria Teresa Helmer Citterich, Mauro Russo, Giandomenico Narducci, Maria Grazia T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title_full | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title_fullStr | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title_full_unstemmed | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title_short | T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
title_sort | t cell leukemia/lymphoma 1a is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171881/ https://www.ncbi.nlm.nih.gov/pubmed/30286151 http://dx.doi.org/10.1371/journal.pone.0204775 |
work_keys_str_mv | AT bresinantonella tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT ragonegianluca tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT cristofoletticristina tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT arcellidiego tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT bassicristian tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT caprinielisabetta tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT fiorenzamariateresa tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT helmercitterichmauro tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT russogiandomenico tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 AT narduccimariagrazia tcellleukemialymphoma1aisessentialformouseepidermalkeratinocytesproliferationpromotedbyinsulinlikegrowthfactor1 |