<i>Podoplanin</i> deficient mice show a rhoa‐related hypoplasia of the sinus venosus myocardium including the sinoatrial node

Mahtab, Edris A F; Vicente‐Steijn, Rebecca; Hahurij, Nathan D.; Jongbloed, Monique R.M.; Wisse, Lambertus J.; DeRuiter, Marco C.; Uhrín, Pavel; Zaujec, Jan; Binder, Bernd R.; Schalij, Martin J.; Poelmann, Robert E.; Groot, Adriana C. Gittenberger‐de

doi:10.1002/dvdy.21819

Cited by 55 publications

(55 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These factors are also important for epicardial-myocardial interaction (PerezPomares et al, 2002;Merki et al, 2005;Winter and Gittenberger-de Groot, 2007). Recently a role for podoplanin and RhoA in this EMT process has been described (Mahtab et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

Bax

Lie-Venema

Vicente‐Steijn

et al. 2009

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

For the establishment of a fully functional septated heart, addition of myocardium from second heart field-derived structures is important. Platelet-derived growth factors (PDGFs) are known for their role in cardiovascular development. In this study, we aim to elucidate this role of PDGF-A, PDGF-C, and their receptor PDGFR-␣. We analyzed the expression patterns of PDGF-A, -C, and their receptor PDGFR-␣ during avian heart development. A spatiotemporal pattern of ligands was seen with colocalization of the PDGFR-␣. This was found in second heart field-derived myocardium as well as the proepicardial organ (PEO) and epicardium. Mechanical inhibition of epicardial outgrowth as well as chemical disturbance of PDGFR-␣ support a functional role of the ligands and the receptor in cardiac development. Developmental Dynamics

show abstract

Section: Introductionmentioning

confidence: 99%

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

Bax

Lie-Venema

Vicente‐Steijn

et al. 2009

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

show abstract

“…22,23 These mice also lack most of the LNs that are replaced by blood-filled, poorly organized remnants. 24 In addition, several cardiac defects, including hypoplasia of the myocardium, were described in podoplanin-deficient embryos, [25][26][27] and deletion of podoplanin at the 2-cell stage causes cerebral hemorrhaging in embryos. 28 The broad expression of podoplanin, together with the lethal phenotype observed in global podoplanin-deficient mice, suggests an important role for podoplanin in diverse cell types and in the ontogeny of different organs.…”

mentioning

confidence: 99%

Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes

Bianchi

Russo

Bachmann

et al. 2017

ATVB

View full text Add to dashboard Cite

Objective-The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. Approach and Results-We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn ΔLEC) and induced gene deletion postnatally. Pdpn ΔLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn ΔLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn ΔLEC mice. Conclusions-These

show abstract

“…It is expressed in several normal cell types and tissues, such as the alveolar epithelium, mesothelia and lymphatic vessels (Schacht et al, 2005;Wicki and Christofori, 2007). Studies with podoplanin-deficient mice suggest that this glycoprotein is involved in lung morphogenesis, lymphatic vasculature formation, and cardiac development (Mahtab et al, 2008(Mahtab et al, , 2009Ramirez et al, 2003;Schacht et al, 2003). Podoplanin expression is upregulated in a variety of cancers, including squamous cell carcinomas and glioblastomas, where it is associated with malignant progression and metastasis ( Astarita et al, 2012;Wicki and Christofori, 2007).…”

Section: Introductionmentioning

confidence: 99%

Podoplanin is a substrate of presenilin-1/γ-secretase

Yurrita¹,

Fernández‐Muñoz²,

Castillo³

et al. 2014

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and -secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transfected with an eGFP-tagged podoplanin construct (PDPNeGFP,(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63) constitutively express two C-terminal fragments (CTFs): a ~3 3 kDa membrane-bound PCTF33, and a ~2 9 kDa cytosolic podoplanin ICD (PICD). While pharmacological inhibition of metalloproteases reduced the expression of PCTF33, treatment of cells with -secretase inhibitors resulted in enhanced PCTF33 levels. PCTF33 processing by -secretase depends on presenilin-1 (PS1) function: cells expressing a dominant negative form of PS1 (PS1 D385N), and mouse embryonic fibroblasts (MEFs) genetically deficient in PS1, but not in PS2, show higher levels of PCTF33 expression with respect to wild-type MEFs. Furthermore, transfection of PS1 deficient MEFs with wild-type PS1 (PS1 wt) decreased PCTF33 levels. N-terminal amino acid sequencing of the affinity purified PICD revealed that the -secretase cleavage site was located between valines 150 and 151, but these residues are not critical for proteolysis. We found that podoplanin CTFs are also generated in cells expressing podoplanin mutants harboring heterologous transmembrane regions. Taken together, these results indicate that podoplanin is a novel substrate for PS1/-secretase.

show abstract

Podoplanin deficient mice show a rhoa‐related hypoplasia of the sinus venosus myocardium including the sinoatrial node

Cited by 55 publications

References 63 publications

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes

Podoplanin is a substrate of presenilin-1/γ-secretase

Contact Info

Product

Resources

About