{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:19:04Z","timestamp":1762157944928,"version":"3.37.3"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["19K22754"],"award-info":[{"award-number":["19K22754"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005611","name":"University of Fukui","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005611","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transgenic Res"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>M-LP\/Mpv17L (Mpv17-like protein) is an atypical cyclic nucleotide phosphodiesterase (PDE) without the molecular structure characteristic of the PDE family. Deficiency of M-LP\/Mpv17L in mice has been found to result in development of \u03b2-cell hyperplasia and improved glucose tolerance. Here, we report another phenotype observed in <jats:italic>M-LP\/Mpv17L<\/jats:italic>-knockout (KO) mice: afferent cardiac hypertrophy. Although the hearts of <jats:italic>M-LP\/Mpv17L<\/jats:italic>-KO mice did not differ in size from those of wild-type mice, there was marked narrowing of the left ventricular lumen and thickening of the ventricular wall. The diameter and cross-sectional area of cardiomyocytes in 8-month-old <jats:italic>M-LP\/Mpv17L<\/jats:italic>-KO mice were increased 1.16-fold and 1.35-fold, respectively, relative to control mice, but showed no obvious abnormalities of cell structure, fibrosis or impaired cardiac function. In 80-day-old KO mice, the expression of hypertrophic marker genes, <jats:italic>brain natriuretic peptide<\/jats:italic> (<jats:italic>BNF<\/jats:italic>), <jats:italic>actin alpha cardiac muscle 1<\/jats:italic> (<jats:italic>ACTC1<\/jats:italic>) and <jats:italic>actin alpha 1 skeletal muscle<\/jats:italic> (<jats:italic>ACTA1<\/jats:italic>), as well as the Wnt\/\u03b2-catenin pathway target genes, <jats:italic>lymphoid enhancer-binding factor-1<\/jats:italic> (<jats:italic>LEF1<\/jats:italic>), <jats:italic>axis inhibition protein 2<\/jats:italic> (<jats:italic>AXIN2<\/jats:italic>) and <jats:italic>transcription factor 7<\/jats:italic> (<jats:italic>TCF7<\/jats:italic>), was significantly up-regulated relative to control mice, whereas fibrosis-related genes such as <jats:italic>fibronectin 1<\/jats:italic> (<jats:italic>FN1<\/jats:italic>) and <jats:italic>connective tissue growth factor<\/jats:italic> (<jats:italic>CTGF<\/jats:italic>) were down-regulated. Western blot analysis revealed increased phosphorylation of molecules downstream of the cAMP\/PKA signaling pathway, such as \u03b2-catenin, ryanodine receptor 2 (RyR2), phospholamban (PLN) and troponin I (cTnI), as well as members of the MEK1-ERK1\/2 signaling pathway, which is strongly involved in afferent cardiac hypertrophy. Taken together, these findings indicate that M-LP\/Mpv17L is one of the PDEs actively functioning in the heart and that deficiency of M-LP\/Mpv17L in mice promotes physiological cardiac hypertrophy.<\/jats:p>","DOI":"10.1007\/s11248-023-00373-7","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T12:02:19Z","timestamp":1697630539000},"page":"575-582","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Knockout of M-LP\/Mpv17L, a newly identified atypical PDE, induces physiological afferent cardiac hypertrophy in mice"],"prefix":"10.1007","volume":"32","author":[{"given":"Reiko","family":"Iida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misuzu","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"373_CR1","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.cell.2015.10.035","volume":"163","author":"K Alkass","year":"2015","unstructured":"Alkass K, Panula J, Westman M et al (2015) No evidence for cardiomyocyte number expansion in preadolescent mice. Cell 163:1026\u20131036. https:\/\/doi.org\/10.1016\/j.cell.2015.10.035","journal-title":"Cell"},{"key":"373_CR2","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.acvd.2016.02.004","volume":"109","author":"P Bobin","year":"2016","unstructured":"Bobin P, Belacel-Ouari M, Bedioune I et al (2016) Cyclic nucleotide phosphodiesterases in heart and vessels: a therapeutic perspective. Arch Cardiovasc Dis 109:431\u2013443. https:\/\/doi.org\/10.1016\/j.acvd.2016.02.004","journal-title":"Arch Cardiovasc Dis"},{"key":"373_CR3","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.1093\/emboj\/19.23.6341","volume":"19","author":"OF Bueno","year":"2000","unstructured":"Bueno OF, De Windt LJ, Tymitz KM et al (2000) The MEK1-ERK1\/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J 19:6341\u20136350. https:\/\/doi.org\/10.1093\/emboj\/19.23.6341","journal-title":"EMBO J"},{"key":"373_CR4","doi-asserted-by":"publisher","first-page":"4610","DOI":"10.1073\/pnas.0835895100","volume":"100","author":"S Haq","year":"2003","unstructured":"Haq S, Michael A, Andreucci M et al (2003) Stabilization of \u03b2-catenin by a wnt-independent mechanism regulates cardiomyocyte growth. Proc Natl Acad Sci USA 100:4610\u20134615. https:\/\/doi.org\/10.1073\/pnas.0835895100","journal-title":"Proc Natl Acad Sci USA"},{"key":"373_CR5","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a037150","volume":"12","author":"TR Heallen","year":"2020","unstructured":"Heallen TR, Kadow ZA, Wang J et al (2020) Determinants of cardiac growth and size. Cold Spring Harb Perspect Biol 12:a037150. https:\/\/doi.org\/10.1101\/cshperspect.a037150","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"373_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118792","volume":"1867","author":"R Iida","year":"2020","unstructured":"Iida R, Ueki M, Yasuda T (2020) Human Mpv17-like protein with a mitigating effect on mtDNA damage is involved in cAMP\/PKA signaling in the mitochondrial matrix. Biochim Biophys Acta Mol Cell Res 1867:118792. https:\/\/doi.org\/10.1016\/j.bbamcr.2020.118792","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"373_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166318","volume":"1868","author":"R Iida","year":"2022","unstructured":"Iida R, Ueki M, Yasuda T (2022) Deficiency of M-LP\/Mpv17L leads to development of \u03b2-cell hyperplasia and improved glucose tolerance via activation of the wnt and TGF-\u03b2 pathways. Biochim Biophys Acta Mol Basis Dis 1868:166318. https:\/\/doi.org\/10.1016\/j.bbadis.2021.166318","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"373_CR8","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0047-6374(99)00104-9","volume":"113","author":"R Iida","year":"2000","unstructured":"Iida R, Yasuda T, Aoyama M et al (2000) Age-related changes of gene expression in mouse kidney: fluorescence differential display-PCR analyses. Mech Ageing Dev 113:135\u2013144. https:\/\/doi.org\/10.1016\/S0047-6374(99)00104-9","journal-title":"Mech Ageing Dev"},{"key":"373_CR9","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1006\/bbrc.2001.4769","volume":"283","author":"R Iida","year":"2001","unstructured":"Iida R, Yasuda T, Tsubota E et al (2001) Cloning, mapping, genomic organization, and expression of mouse M-LP, a new member of the peroxisomal membrane protein Mpv17 domain family. Biochem Biophys Res Commun 283:292\u2013296. https:\/\/doi.org\/10.1006\/bbrc.2001.4769","journal-title":"Biochem Biophys Res Commun"},{"key":"373_CR10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cell.2005.07.030","volume":"123","author":"SE Lehnart","year":"2005","unstructured":"Lehnart SE, Wehrens XH, Reiken S et al (2005) Phosphodiesterase4D deficiency in the ryanodine-receptor complex promotesheart failure and arrhythmias. Cell 123:25\u201335","journal-title":"Cell"},{"key":"373_CR11","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1007\/s11886-022-01756-8","volume":"24","author":"D Li","year":"2022","unstructured":"Li D, Sun J, Zhong TP (2022) WNT signaling in heart development and regeneration. Curr Cardiol Rep 24:1425\u20131438. https:\/\/doi.org\/10.1007\/s11886-022-01756-8","journal-title":"Curr Cardiol Rep"},{"key":"373_CR12","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1242\/jcs.140251","volume":"127","author":"D Mika","year":"2014","unstructured":"Mika D, Richter W, Westenbroek RE et al (2014) PDE4B mediates local feedback regulation of \u03b21-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes. J Cell Sci 127:1033\u20131042. https:\/\/doi.org\/10.1242\/jcs.140251","journal-title":"J Cell Sci"},{"key":"373_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1157043","volume":"14","author":"B Ni","year":"2023","unstructured":"Ni B, Sun M, Zhao J et al (2023) The role of \u03b2-catenin in cardiac diseases. Front Pharmacol 14:1157043. https:\/\/doi.org\/10.3389\/fphar.2023.1157043","journal-title":"Front Pharmacol"},{"key":"373_CR14","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1161\/01.RES.0000256354.95791.f1","volume":"100","author":"K Omori","year":"2007","unstructured":"Omori K, Kotera J (2007) Overview of PDEs and their regulation. Circ Res 100:309\u2013327. https:\/\/doi.org\/10.1161\/01.RES.0000256354.95791.f1","journal-title":"Circ Res"},{"key":"373_CR15","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.yjmcc.2007.06.006","volume":"43","author":"J Qu","year":"2007","unstructured":"Qu J, Zhou J, Yi XP et al (2007) Cardiac-specific haploinsufficiency of beta-catenin attenuates cardiac hypertrophy but enhances fetal gene expression in response to aortic constriction. J Mol Cell Cardiol 43:319\u2013326. https:\/\/doi.org\/10.1016\/j.yjmcc.2007.06.006","journal-title":"J Mol Cell Cardiol"},{"key":"373_CR16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00125-007-0848-0","volume":"51","author":"S Schinner","year":"2008","unstructured":"Schinner S, Ulgen F, Papewalis C et al (2008) Regulation of insulin secretion, glucokinase gene transcription and beta cell proliferation by adipocyte-derived wnt signalling molecules. Diabetologia 51:147\u2013154. https:\/\/doi.org\/10.1007\/s00125-007-0848-0","journal-title":"Diabetologia"},{"key":"373_CR17","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/ng1765","volume":"38","author":"A Spinazzola","year":"2006","unstructured":"Spinazzola A, Viscomi C, Fernandez-Vizarra E et al (2006) MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet 38:570\u2013575. https:\/\/doi.org\/10.1038\/ng1765","journal-title":"Nat Genet"},{"key":"373_CR18","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1161\/CIRCULATIONAHA.106.679589","volume":"116","author":"Y Wang","year":"2007","unstructured":"Wang Y (2007) Mitogen-activated protein kinases in heart development and diseases. Circulation 116:1413\u20131423. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.106.679589","journal-title":"Circulation"}],"container-title":["Transgenic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11248-023-00373-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11248-023-00373-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11248-023-00373-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T21:43:01Z","timestamp":1702330981000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11248-023-00373-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,18]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["373"],"URL":"https:\/\/doi.org\/10.1007\/s11248-023-00373-7","relation":{},"ISSN":["0962-8819","1573-9368"],"issn-type":[{"type":"print","value":"0962-8819"},{"type":"electronic","value":"1573-9368"}],"subject":[],"published":{"date-parts":[[2023,10,18]]},"assertion":[{"value":"31 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}