EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.

Placental lactogen (PL) induced serotonergic signaling is essential for gestational β-cell mass expansion. We have previously shown that intact Epidermal growth factor -receptor (EGFR) function is a crucial component of this pathway. We now explored more specifically the link between EGFR and pregna...

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Autores principales:	Elina Hakonen, Jarkko Ustinov, Jaan Palgi, Päivi J Miettinen, Timo Otonkoski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/002075132668414f9f07773864b4e741
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spelling	oai:doaj.org-article:002075132668414f9f07773864b4e7412021-11-18T08:25:13ZEGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.1932-620310.1371/journal.pone.0093651https://doaj.org/article/002075132668414f9f07773864b4e7412014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24695557/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Placental lactogen (PL) induced serotonergic signaling is essential for gestational β-cell mass expansion. We have previously shown that intact Epidermal growth factor -receptor (EGFR) function is a crucial component of this pathway. We now explored more specifically the link between EGFR and pregnancy-induced β-cell mass compensation. Islets were isolated from wild-type and β-cell-specific EGFR-dominant negative mice (E1-DN), stimulated with PL and analyzed for β-cell proliferation and expression of genes involved in gestational β-cell growth. β-cell mass dynamics were analyzed both with traditional morphometrical methods and three-dimensional optical projection tomography (OPT) of whole-mount insulin-stained pancreata. Insulin-positive volume analyzed with OPT increased 1.4-fold at gestational day 18.5 (GD18.5) when compared to non-pregnant mice. Number of islets peaked by GD13.5 (680 vs 1134 islets per pancreas, non-pregnant vs. GD13.5). PL stimulated beta cell proliferation in the wild-type islets, whereas the proliferative response was absent in the E1-DN mouse islets. Serotonin synthesizing enzymes were upregulated similarly in both the wild-type and E1-DN mice. However, while survivin (Birc5) mRNA was upregulated 5.5-fold during pregnancy in the wild-type islets, no change was seen in the E1-DN pregnant islets. PL induced survivin expression also in isolated islets and this was blocked by EGFR inhibitor gefitinib, mTOR inhibitor rapamycin and MEK inhibitor PD0325901. Our 3D-volumetric analysis of β-cell mass expansion during murine pregnancy revealed that islet number increases during pregnancy. In addition, our results suggest that EGFR signaling is required for lactogen-induced survivin expression via MAPK and mTOR pathways.Elina HakonenJarkko UstinovJaan PalgiPäivi J MiettinenTimo OtonkoskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e93651 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elina Hakonen Jarkko Ustinov Jaan Palgi Päivi J Miettinen Timo Otonkoski EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
description	Placental lactogen (PL) induced serotonergic signaling is essential for gestational β-cell mass expansion. We have previously shown that intact Epidermal growth factor -receptor (EGFR) function is a crucial component of this pathway. We now explored more specifically the link between EGFR and pregnancy-induced β-cell mass compensation. Islets were isolated from wild-type and β-cell-specific EGFR-dominant negative mice (E1-DN), stimulated with PL and analyzed for β-cell proliferation and expression of genes involved in gestational β-cell growth. β-cell mass dynamics were analyzed both with traditional morphometrical methods and three-dimensional optical projection tomography (OPT) of whole-mount insulin-stained pancreata. Insulin-positive volume analyzed with OPT increased 1.4-fold at gestational day 18.5 (GD18.5) when compared to non-pregnant mice. Number of islets peaked by GD13.5 (680 vs 1134 islets per pancreas, non-pregnant vs. GD13.5). PL stimulated beta cell proliferation in the wild-type islets, whereas the proliferative response was absent in the E1-DN mouse islets. Serotonin synthesizing enzymes were upregulated similarly in both the wild-type and E1-DN mice. However, while survivin (Birc5) mRNA was upregulated 5.5-fold during pregnancy in the wild-type islets, no change was seen in the E1-DN pregnant islets. PL induced survivin expression also in isolated islets and this was blocked by EGFR inhibitor gefitinib, mTOR inhibitor rapamycin and MEK inhibitor PD0325901. Our 3D-volumetric analysis of β-cell mass expansion during murine pregnancy revealed that islet number increases during pregnancy. In addition, our results suggest that EGFR signaling is required for lactogen-induced survivin expression via MAPK and mTOR pathways.
format	article
author	Elina Hakonen Jarkko Ustinov Jaan Palgi Päivi J Miettinen Timo Otonkoski
author_facet	Elina Hakonen Jarkko Ustinov Jaan Palgi Päivi J Miettinen Timo Otonkoski
author_sort	Elina Hakonen
title	EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
title_short	EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
title_full	EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
title_fullStr	EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
title_full_unstemmed	EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.
title_sort	egfr signaling promotes β-cell proliferation and survivin expression during pregnancy.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/002075132668414f9f07773864b4e741
work_keys_str_mv	AT elinahakonen egfrsignalingpromotesbcellproliferationandsurvivinexpressionduringpregnancy AT jarkkoustinov egfrsignalingpromotesbcellproliferationandsurvivinexpressionduringpregnancy AT jaanpalgi egfrsignalingpromotesbcellproliferationandsurvivinexpressionduringpregnancy AT paivijmiettinen egfrsignalingpromotesbcellproliferationandsurvivinexpressionduringpregnancy AT timootonkoski egfrsignalingpromotesbcellproliferationandsurvivinexpressionduringpregnancy
_version_	1718421781879980032

EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy.

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