Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a pre...

The activation of the microvascular endothelial cell platelet-derived growth factor (PDGF) receptor (PDGF-R) by PDGF has been implicated in neoplastic angiogenesis. Here, we established cultures of murine bone microvascular endothelial cells and examined their response to stimulation with PDGF BB ligand and to blockade of PDGF-R signaling with the tyrosine kinase inhibitor STI571 (Gleevec). The...

Platelet-derived growth factor (PDGF)- A-deficient male mice were found to develop progressive reduction of testicular size, Leydig cells loss, and spermatogenic arrest. In normal mice, the PDGF-A and PDGF-Ralpha expression pattern showed positive cells in the seminiferous epithelium and in interstitial mesenchymal cells, respectively. The testicular defects seen in PDGF-A-/- mice, combined wit...

Although altered expression of platelet-derived growth factor (PDGF)A is a hallmark of many cancers, the importance of pro-PDGF-A conversion to PDGF-A in tumorigenesis and the cognate protease(s) is unknown. Pro-PDGF-A processing occurs at pairs of basic residues, likely involving the proprotein convertases (PCs). In the colon carcinoma cell line LoVo, we found that Furin is the most potent PDG...

Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colo...

Platelet-derived growth factor (PDGF) signals through several pathways, including mitogen-activated protein (MAP) kinase, Jun kinase, and C kinase, and stimulates proliferation of fibroblasts. Pentoxifylline inhibits PDGF-driven proliferation of fibroblasts. We have reported that pentoxifylline did not inhibit binding of PDGF to its specific cell-surface receptors or PDGF receptor phosphorylati...

STUDY DESIGN Preclinical animal study. OBJECTIVE Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration. SUMMARY OF BACKGROUND DATA IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated t...

Muscarinic receptors and platelet-derived growth factor (PDGF) receptors synergistically induce proliferation of airway smooth muscle (ASM), but the pathways that regulate these effects are not yet completely identified. We hypothesized that glycogen synthase kinase-3 (GSK-3), a kinase that represses several promitogenic signaling pathways in its unphosphorylated form, is cooperatively inhibite...

A series of nontransformed human and murine cells and derivative cell lines transformed by methylcholanthrene; by simian virus 40, Kirsten and Moloney murine sarcoma viruses, simian sarcoma virus, and adenovirus; and by a "spontaneous" event in culture were examined for the expression of receptors for the platelet-derived growth factor (PDGF) and for production of substances able to compete wit...

Prostate carcinoma cell lines DU-145 and PC-3 express both platelet derived growth factor (PDGF)-1 and PDGF-2/sis genes. Concomitantly, these cells synthesize and secrete PDGF-like proteins, as judged by indirect immunofluorescence and by direct immunoprecipitation with specific PDGF antiserum. Conditioned media derived from DU-145 and PC-3 cells stimulated the incorporation of [3H]thymidine by...