Biomedical subjects

M Pekny

Publications and source records attributed to M Pekny.

5 recordsLinked to original sources

PubMed1996

PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.

A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.

Actins↗

PubMed1996

Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein.

In the prion diseases, extensive reactive gliosis is often found to be out of proportion to the degree of apparent neuronal damage. To evaluate the role of astrocytic gliosis in experimental scrapie of the mouse, we inoculated mice deficient in apolipoprotein E (apoE) or the glial fibrillary acidic protein (GFAP) with mouse prions. The expression of both apoE and GFAP in astrocytes increases as part of the reactive gliosis that accompanies scrapie. Null mice deficient in either apoE or GFAP inoculated with prions exhibited incubation times indistinguishable from untargeted control mice. The level of PrPSc and its regional deposition in the brains of ill mice deficient in either protein were also similar to control mice. Our findings demonstrate that neither apoE nor GFAP participates in the pathogenesis of the disease or in the production of PrPSc.

Animals↗

PubMed1995

Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally.

Glial fibrillary acidic protein (GFAP) is the main component of the intermediate filaments in cells of astroglial lineage, including astrocytes in the CNS, nonmyelin forming Schwann cells and enteric glia. To address the function of GFAP in vivo, we have disrupted the GFAP gene in mice via targeted mutation in embryonic stem cells. Mice lacking GFAP developed normally, reached adulthood and reproduced. We did not find any abnormalities in the histological architecture of the CNS, in their behavior, motility, memory, blood-brain barrier function, myenteric plexi histology or intestinal peristaltic movement. Comparisons between GFAP and S-100 immunohistochemical staining patterns in the hippocampus of wild-type and mutant mice suggested a normal abundance of astrocytes in GFAP-negative mice, however, in contrast to wild-types, GFAP-negative astrocytes of the hippocampus and in the white matter of the spinal cord were completely lacking intermediate filaments. This shows that the loss of GFAP intermediate filaments is not compensated for by the up-regulation of other intermediate filament proteins, such as vimentin. The GFAP-negative mice displayed post-traumatic reactive gliosis, which suggests that GFAP up-regulation, a hallmark of reactive gliosis, is not an obligatory requirement for this process.

Animals↗

PubMed1994

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.

Platelet-derived growth factor (PDGF) affects the growth, migration, and function in vitro of mesenchymal cells, but little is known about its normal physiological functions in vivo. We show here that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. Instead, a single or a few distended capillary loops fill the glomerular space. The heart and some large arteries dilate in late-stage embryos. Most PDGF B mutant embryos develop fatal hemorrhages just prior to birth. Their hematological status includes erythroblastosis, macrocytic anemia, and thrombocytopenia. On the basis of these findings, we conclude that PDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.

Anemia↗

PubMed1994

Differences in binding to the solid substratum and extracellular matrix may explain isoform-specific paracrine effects of platelet-derived growth factor.

We have studied the paracrine response of fibroblasts to the two homodimeric isoforms of platelet-derived growth factor (PDGF-AA and -BB). CHO-cells stably transfected with a B-chain cDNA expression vector (CHO-PDGF-B cells), were found to elicit a marked paracrine response when seeded at clonal density on preformed monolayers of human or murine fibroblasts; no such response was elicited by CHO-PDGF-A cells. Immunofluorescence microscopy of CHO-PDGF-B cell cultures showed the presence of a pericellular deposit of material reacting with antibodies against PDGF-BB; no corresponding PDGF-AA immunoreactive material was found in the CHO-PDGF-A cultures. The pericellular material, deposited by CHO-PDGF-B cells, was shown to have a growth promoting effect on target cells. Furthermore, we could show that 125I-PDGF-BB binds more efficiently than 125I-PDGF-AA to extracellular matrix prepared from foreskin fibroblast cultures, as well as to defined extracellular matrix components (fibronectin, laminin and collagen III). The results reveal a marked difference in the paracrine activity of PDGF-AA and PDGF-BB; the latter has a strong local growth enhancing effect, that is mostly likely to be ascribed to its association with components of the extracellular matrix.

3T3 Cells↗