Disease relevance of Pdpn

• Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis [1].
• To indicate that this protein could be associated with transformation of arborized foot processes to flat feet (Latin, pes planus) we have called it podoplanin [1].
• Lymphatic microvessels in the rat remnant kidney model of renal fibrosis: aminopeptidase p and podoplanin are discriminatory markers for endothelial cells of blood and lymphatic vessels [2].
• T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema [3].
• T1alpha/podoplanin(-/-) mice die at birth due to respiratory failure and have defects in lymphatic, but not blood vessel pattern formation [3].

High impact information on Pdpn

• We show that while retinal ganglion cells from embryonic day 6 (E6) chicks extend profuse neurites on laminin, those from E11 do not, although they retain the ability to extend neurites on astrocytes via a laminin-independent mechanism [4].
• However, no VIP mRNA was detected in the E11 rat embryo or embryonic membranes by in situ hybridization or reverse transcriptase-PCR [5].
• In the present study, the embryonic day (E11) rat embryo/trophoblast was shown to have four times the VIP concentration of the E17 fetus and to have VIP receptors in the central nervous system [5].
• T1alpha/podoplanin is first expressed at around E11.0 in Prox1-positive lymphatic progenitor cells, with predominant localization in the luminal plasma membrane of lymphatic endothelial cells during later development [3].
• Neurite outgrowth by retinal neurons from embryonic day 7 (E7) and E11 chick embryos depended on the function of a calcium-dependent cell adhesion molecule (N-cadherin) and beta 1-class integrin extracellular matrix receptors [6].

Chemical compound and disease context of Pdpn

• CONCLUSIONS: These data support the authors' previous finding that Adriamycin induces notochord hypertrophy and suggest that notochord volume is increased relative to embryo volume soon after Adriamycin administration and is maximal on E11 [7].

Biological context of Pdpn

• Three exons encode the predicted RTI40 extracellular domain and one encodes the single transmembrane spanning domain [8].
• The cDNA encoding the E11 antigen was cloned from a cDNA library prepared from ROS 17/2.8 cells, using a eukaryotic expression system [9].
• We have analyzed the effect of triiodothyronine and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on expression of the transformed phenotype, as monitored by agar clonigenicity, in a single cell clone of type 5 adenovirus-transformed Sprague-Dawley rat embryo cells, E11, and a nude mouse tumor-derived E11 subclone, E11-NMT [10].
• GAD65 and GAD67 mRNAs were detected at E11 and increased exponentially over three orders of magnitude during embryonic development, then declined approximately threefold in the first-2 postnatal weeks [11].
• AS2 and E11 inhibited serum-inducible [(3)H]thymidine incorporation into DNA, as well as serum stimulation of total cell numbers [12].

Anatomical context of Pdpn

• Characterization of the gene and promoter for RTI40, a differentiation marker of type I alveolar epithelial cells [8].
• Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes [9].
• RTI40 is a 40-42 kDa protein that, within the lung, is specific to the apical plasma membrane of the rat alveolar type I cell [13].
• THase was localized in cells of the brain of the same rat fetuses beginning on day E12 (no THase was detected on day E11 or E11.5) in the mantle layer of the ventral mesencephalic and rostrolateral rhombocephalic cellular groups; however [14].
• In the spinal cord, stage-specific-neurite-associated proteins (SNAP) expression occurs first along motor axon pathways on embryonic day (E) 10 and then within the nerve trunks of dorsal root ganglia and the commissural fiber system on E11 [15].

Associations of Pdpn with chemical compounds

• Analysis of purified RTI40 shows that the protein contains glycan, some of which is sialic acid [13].
• In contrast, the presence or absence of triiodothyronine did not alter the population doubling time or saturation density of E11 or E11-NMT cells [10].
• We previously reported an activity termed netrin-synergizing activity (NSA) that can potentiate the outgrowth-promoting activity of netrin-1 on E11 explants (Serafini et al.). Here we report a biochemical characterization of NSA in netrin-depleted high salt extracts of E10 chicken brain membranes [16].
• A single-exposure of B1/PKC cells to 5-azacytidine (AZA), followed by growth in the absence of this demethylating agent, results in B1/PKC-AZA clones which display a stable reversion of the progression phenotype to that of the unprogressed parental E11 clone [17].
• Pregnant rats on embryonic day 8 (E8), E11, E13, E16, E18 or E21 were treated orally with a single administration of 20 mg/kg methylmercury chloride, and the brains of their delivered offspring were examined on postnatal day 7 (P7) and P28 [18].

Other interactions of Pdpn

• Examined by nuclear run-on assays, mechanical distention caused changes in transcriptional rates of RTI 40, SP-B, and SP-C [19].

Analytical, diagnostic and therapeutic context of Pdpn

• By RT-PCR T1 alpha is detected in rat lung from Day 13.5 onward, but is detected by in situ hybridization earlier in lung, brain and neural derivatives, and foregut [20].
• RT-PCR analysis shows expression of T1 alpha in freshly isolated type I cells (50-60% purity) but not in highly purified type II cells or other lung cells [20].
• The cDNA for T1 alpha is 1.85 kb and identifies a single mRNA species of the same size on Northern blots of adult rat lung [20].
• Western blot analysis revealed that two oligonucleotides, AS2 and E11, inhibited Egr-1 synthesis in cells exposed to serum without affecting levels of the zinc finger protein Sp1 [12].
• To this aim, pregnant NHE and random-bred females received a subcutaneous injection of AM-404 (1 mg/kg) or vehicle daily from E11 until E20 [21].

References