Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the importance of the transcription factor Pax3 has been identified in many embryological processes including neural crest cell migration, neural tube closure, and limb muscle formation, its role in proper formation of the ribs has not been well characterized. We have used the Splotch mouse which has a mutation in the Pax3 gene to determine what role Pax3 may play in rib morphogenesis. Homozygous Splotch embryos collected from days 13.5 to 16.5 of gestation displayed severe rib abnormalities including fusions at both the proximal and distal regions. Given its expression in the dermomyotome, we sought to determine when Pax3 expression in the Splotch mutant initially becomes abnormal and which rib segment progenitors may be affected. Prior to somite differentiation at 9.5 dpc (days post coitum), Pax3 is normally expressed in the somites; after differentiation, however, Pax3 expression is diminished in Splotch embryos. We also determined that significantly increased levels of apoptosis occur in the thoracic region by 11.0 dpc relative to wild-type littermates. Because Patch mouse mutants which fail to express PDGF alpha-receptor also have rib abnormalities, we sought to determine whether Pax3 may influence the expression of this receptor. By in situ hybridization, we determined that initially the expression of PDGFRalpha is normal in Splotch mutants at 10.0 dpc, but decreases by 12.5 dpc in the thoracic somite region, suggesting that Pax3 may act upstream of PDGFRalpha. Taken together, our results show that Pax3 expression is important for normal rib development and that increased apoptosis occurs in the thoracic muscles. We suggest that Pax3 may influence the expression of PDGFRalpha, and that the reduced and/or deficient thoracic muscles may contribute to the resulting rib abnormalities.
Anat Rec 1999 07 01
PMID:Abnormal skeletogenesis occurs coincident with increased apoptosis in the Splotch (Sp2H) mutant: putative roles for Pax3 and PDGFRalpha in rib patterning. 1041 2

Platelet-derived growth factor-A and its receptor, platelet-derived growth factor receptor-alpha (PDGF-Ralpha), are required for formation of the secondary pulmonary alveolar septa in mice. However, it remains unclear how these molecules direct the secondary septation process. We have examined the abundance, location, and the accumulation of alpha-smooth muscle actin (alphaSMA), neutral lipid droplets, and elastin in the proximity of PDGF-Ralpha-expressing alveolar cells during postnatal days 4 through 12 in the mouse. PDGF-Ralpha-expressing cells preferentially have characteristics of myofibroblasts and were more likely to contain alphaSMA than are alveolar cells that do not express PDGF-Ralpha. PDGF-Ralpha expressing cells were preferentially located in the alveolar entry ring (AER) where alphaSMA and elastic fibers accumulate. In contrast, PDGF-Ralpha expression inversely correlated with neutral lipid accumulation, which was more prominent at the alveolar base, distant from the AER. PDGF-Ralpha-expressing alveolar cells accumulate in the AER where they may promote mechanical stability during respiration. In addition to defining how alveolar septa form, these findings may have implications for the treatment of diseases which involve alveolar effacement such as emphysema and pulmonary fibrosis.
Anat Rec (Hoboken) 2008 Dec
PMID:Platelet-derived growth factor receptor-alpha-expressing cells localize to the alveolar entry ring and have characteristics of myofibroblasts during pulmonary alveolar septal formation. 1883 69

Peroxisome proliferator-activated receptor (PPAR)-gamma is reduced in pulmonary arteries (PAs) of patients with PA hypertension (PAH), and we reported that deletion of PPARgamma in smooth muscle cells (SMCs) of transgenic mice results in PAH. However, the sequelae of loss of PPARgamma in PA endothelial cells (ECs) are unknown. Therefore, we bred Tie2-Cre mice with PPARgamma(flox/flox) mice to induce EC loss of PPARgamma (Tie2 PPARgamma(-/-)), and we assessed PAH by right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and muscularized distal PAs in room air (RA), after chronic hypoxia (CH), and after 4 wk of recovery in RA (Rec-RA). The Tie2 PPARgamma(-/-) mice developed spontaneous PAH in RA with increased RVSP, RVH, and muscularized PAs vs. wild type (WT); both genotypes exhibited a similar degree of PAH following chronic hypoxia, but Tie2 PPARgamma(-/-) mice had more residual PAH compared with WT mice after Rec-RA. The Tie2 PPARgamma(-/-) vs. WT mice in RA had increased platelet-derived growth factor receptor-beta (PDGF-Rbeta) expression and signaling, despite an elevation in the PPARgamma target apolipoprotein E, an inhibitor of PDGF signaling. Inhibition of PDGF-Rbeta signaling with imatinib, however, was sufficient to reverse the PAH observed in the Tie2 PPARgamma(-/-) mice. Thus the disruption of PPARgamma signaling in EC is sufficient to cause mild PAH and to impair recovery from CH-induced PAH. Inhibition of heightened PDGF-Rbeta signaling is sufficient to reverse PAH in this genetic model.
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PMID:Tie2-mediated loss of peroxisome proliferator-activated receptor-gamma in mice causes PDGF receptor-beta-dependent pulmonary arterial muscularization. 1980 50

The basement membrane zone (BMZ) appears as three component layers: the lamina lucida, lamina densa, and lamina reticularis. The laminas lucida and densa are present during all stages of development. The lamina reticularis appears during postnatal development. Collagens I, III, and V form heterogeneous fibers that account for the thickness of the lamina reticularis. Additionally, there are three proteoglycans considered as integral components of the BMZ: perlecan, collagen XVIII, and bamacan. Perlecan is the predominant heparan sulfate proteoglycan in the airway BMZ. It is responsible for many of the functions attributed to the BMZ, in particular, trafficking of growth factors and cytokines between epithelial and mesenchymal cells. Growth factor binding sites on perlecan include FGF-1, FGF-2, FGF-7, FGF-10, PDGF, HGF, HB-EGF, VEGF, and TGF-beta. Growth factors pass through the BMZ when moving between the epithelial and mesenchymal cell layers. They move by rapid reversible binding with sites on both the heparan sulfate chains and core protein of perlecan. In this manner, perlecan regulates movement of growth factors between tissues. Another function of the BMZ is storage and regulation of FGF-2. FGF-2 has been shown to be involved with normal growth and thickening of the BMZ. Thickening of the BMZ is a feature of airway remodeling in asthma. It may have a positive effect by protecting against airway narrowing and air trapping. Conversely, it may have a negative effect by influencing trafficking of growth factors in the epithelial mesenchymal trophic unit. However, currently the significance of BMZ thickening is not known.
Anat Rec (Hoboken) 2010 Jun
PMID:Postnatal development of the lamina reticularis in primate airways. 2050 89