| http://purl.uniprot.org/citations/23941874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23941874 | http://www.w3.org/2000/01/rdf-schema#comment | "A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species, DFs also displayed a significant increase in senescence-associated β-galactosidase activity and phospho-γ-histone H2AX (pH2AX) level. Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes. Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. Most of the aforementioned oxidative stress and senescence-based features observed in DFs were recapitulated in a 10-day-old diabetic wound. Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNA- or Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state. Overall, our data illuminate Cav-1/PTRF-1 as a key player of a novel signaling pathway that may link a heightened state of oxidative stress to cellular senescence and impaired wound healing in diabetes."xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpendo.00189.2013"xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/author | "Abdel-Halim S.M."xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/author | "Al-Mulla F."xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/author | "Bitar M.S."xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/name | "Am J Physiol Endocrinol Metab"xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/pages | "E951-63"xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/title | "Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes."xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://purl.uniprot.org/core/volume | "305"xsd:string |
| http://purl.uniprot.org/citations/23941874 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23941874 |
| http://purl.uniprot.org/citations/23941874 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23941874 |
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