Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts

Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1α protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1α (HIF-1α) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1α may be a novel therapeutic target to modulate the scar fibrosis process

Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts

Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1α protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1α (HIF-1α) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1α may be a novel therapeutic target to modulate the scar fibrosis process

Clock-Comparison Tests of Lorentz and CPT Symmetry in Space

Clock-comparison experiments conducted in space can provide access to many unmeasured coefficients for Lorentz and CPT violation. The orbital configuration of a satellite platform and the relatively large velocities attainable in a deep-space mission would permit a broad range of tests with Planck-scale sensitivity.Comment: 4 page

Constraints on Lorentz violation from clock-comparison experiments

Constraints from clock-comparison experiments on violations of Lorentz and CPT symmetry are investigated in the context of a general Lorentz-violating extension of the standard model. The experimental signals are shown to depend on the atomic and ionic species used as clocks. Certain experiments usually regarded as establishing comparable bounds are in this context sensitive to different types of Lorentz violation. Some considerations relevant to possible future measurements are presented. All these experiments are potentially sensitive to Lorentz-violating physics at the Planck scale.Comment: accepted for publication in Physical Review D; scheduled for issue of December 1, 199

One-Loop Renormalization of Lorentz-Violating Electrodynamics

We show that the general Lorentz- and CPT-violating extension of quantum electrodynamics is one-loop renormalizable. The one-loop Lorentz-violating beta functions are obtained, and the running of the coefficients for Lorentz and CPT violation is determined. Some implications for theory and experiment are discussed.Comment: 12 pages, accepted for publication in Physical Review

Probing Lorentz and CPT violation with space-based experiments

Space-based experiments offer sensitivity to numerous unmeasured effects involving Lorentz and CPT violation. We provide a classification of clock sensitivities and present explicit expressions for time variations arising in such experiments from nonzero coefficients in the Lorentz- and CPT-violating Standard-Model Extension.Comment: 15 page

Frequent Mutations of p53 and MTS1/CDK4I Tumor Suppressor Genes in Chinese Preneoplastic and Neoplastic Oral Tissues

This study is, in part, supprtred by grants from the Smokeless Tobacoo Research Council, Inc.(Number 0231) and USPHS research grants P50 DE100598 and RO1 DE10049 from the National Institute of Dental Research, NIH