Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endostatin, a proteolytic fragment of type XVIII collagen, has been shown to inhibit angiogenesis, tumor growth, and endothelial cell proliferation and migration. We analyzed its functions in vivo by generating transgenic mice in which it was overexpressed in the skin and lens capsule under the keratin K14 promoter. Opacity of the lens occurred at 4 months of age in the mouse line J4, with the highest level of endostatin expression. The lens epithelial cells appeared to lose contact with the capsule and began to vacuolize. In 1-year-old mice the lens epithelial cell layer had entirely degenerated, and instead, large plaques of spindle-shaped cells had formed in the anterior region of the lens. Moreover, a widening of the epidermal basement membrane (BM) zone of the skin was observed in electron microscopy. The epidermal BM was conspicuously altered in the J4 mice with high transgene expression, including clear broadening and occurrence of pearl-like protrusions in some areas, whereas the BM was more even in appearance but consistently broadened in the mouse line G20 with moderate transgene expression. In both lines the BM was continuous. Measurements indicated that the lamina densa was 78.54 +/- 53.10 nm in line J4, the large variation reflecting the protrusions of the lamina densa, and 44.24 +/- 11.52 nm in line G20, compared with 33.74 +/- 9.96 nm in wild-type adult mice. Immunoelectron microscopy of wild-type mouse skin type XVIII collagen showed a polarized orientation in the BMs, with the C-terminal endostatin region localized in the lamina densa and the N terminus in average approximately 40 nm more on the dermal side. Type XVIII collagen was dispersed in the transgenic skin, suggesting that the transgene-derived endostatin fragment displaces the full-length collagen XVIII. This may impair the anchoring of the lamina densa to the dermis and thereby lead to loosening of the BMs, resembling the previously observed situation in collagen XVIII-null mice.
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PMID:Endostatin overexpression specifically in the lens and skin leads to cataract and ultrastructural alterations in basement membranes. 1563 14

Noninvasive detection of dysplasia provides a potential platform for monitoring the efficacy of chemopreventive therapy of premalignancy, imaging the tissue compartments comprising dysplasia: epithelium, microvasculature, and stromal inflammatory cells. Here, using respiratory-gated magnetic resonance imaging (MRI), the anatomy of premalignant and malignant stages of cervical carcinogenesis in estrogen-treated K14-HPV16 transgenic mice was noninvasively defined. Dynamic contrast enhanced (DCE)-MRI was used to quantify leakage across premalignant dysplastic microvasculature. Vascular permeability as measured by DCE-MRI, K(trans), was similar in transgenic (0.053 +/- 0.020 min(-1); n = 32 mice) and nontransgenic (0.056 +/- 0.029 min(-1); n = 17 mice) animals despite a 2-fold increase in microvascular area in the former compared with the latter. DCE-MRI did detect a significant decrease in vascular permeability accompanying diminution of dysplastic microvasculature by the antiangiogenic agent, vascular endothelial growth factor Trap (K(trans) = 0.052 +/- 0.013 min(-1) pretreatment; n = 6 mice versus K(trans) = 0.019 +/- 0.008 min(-1) post-treatment; n = 5 mice). Thus, we determined that the threshold of microvessel leakage associated with cervical dysplasia was <17 kDa and highlighted the potential of DCE-MRI to noninvasively monitor the efficacy of antiangiogenic drugs or chemoprevention regimens targeting the vasculature in premalignant cervical dysplasia.
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PMID:Magnetic resonance imaging defines cervicovaginal anatomy, cancer, and VEGF trap antiangiogenic efficacy in estrogen-treated K14-HPV16 transgenic mice. 1978 43

Skin-derived precursors (SKPs) can differentiate into fibroblasts. However, little is known about the molecular mechanism of the differentiation process. Our previous study has compared the transcriptomes of mouse SKPs and SKP-derived fibroblasts (SFBs) by RNA-Seq analysis and found some genes and signal pathways that might play important roles in the transition from SKPs to SFBs. Here, to further investigate the process by which SKPs differentiate into fibroblasts, we compared the proteomes between SKPs and SFBs using iTRAQ. Our results showed that 243 differentially expressed proteins (DEPs) were identified. Among the 28 DEPs which were related to the functional group of cell differentiation, Down-regulated DEPs collagen XVIII, keratin 10, keratin 5, keratin 14, and TIFIbeta, up-regulated DEPs Thy-1, ANXA1, alpha-catenin, and calreticulin might play important roles in the transition of SKPs to fibroblasts. Further study is needed to clarify the roles of these proteins in the differentiation process of SKPs into fibroblasts, which could facilitate investigations of the detailed molecular mechanisms in the process and make it possible to take advantage of the potential therapeutic applications of SKPs in skin regeneration in the future.
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PMID:Comparison of the proteomes of mouse Skin Derived Precursors (SKPs) and SKP-derived fibroblasts (SFBs) by iTRAQ. 2874 44