Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.

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Karbalaei, MardjanehLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology (author)

Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.

Article/chapterEnglish2015

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2015-01-24
Public Library of Science (PLoS),2015
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LIBRIS-ID:oai:lup.lub.lu.se:b5d6ac7a-884e-4328-8359-a6d9389360c3
https://lup.lub.lu.se/record/5039800URI
https://doi.org/10.1371/journal.pone.0116784DOI

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Language:English
Summary in:English

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The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of miR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the miR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced miR-132/212 in human detrusor cells. To identify miR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between miR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases miR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.

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Ekman, MariLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology(Swepub:lu)fkem-mpe (author)
Krawczyk, KatarzynaLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups(Swepub:lu)med-kkw (author)
Svensson, DanielLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)med-dis (author)
Göransson, OlgaLund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups(Swepub:lu)medk-ogo (author)
Dahan, DianaLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups(Swepub:lu)med-ddn (author)
Nilsson, Bengt-OlofLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-bon (author)
Albinsson, SebastianLund University,Lunds universitet,Kärlfysiologi,Forskargrupper vid Lunds universitet,Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-sal (author)
Uvelius, BengtLund University,Lunds universitet,Urologi,Forskargrupper vid Lunds universitet,Urology,Lund University Research Groups(Swepub:lu)uro-buv (author)
Swärd, KarlLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Kärlfysiologi,Cellular Biomechanics,Lund University Research Groups,Vascular Physiology(Swepub:lu)mphy-ksw (author)
Cellulär biomekanikForskargrupper vid Lunds universitet (creator_code:org_t)

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In:PLoS ONE: Public Library of Science (PLoS)10:11932-6203

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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