Keratinocyte-Targeted Overexpression of the Glucocorticoid Receptor Delays Cutaneous Wound Healing

Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC) analogs, which act through the ligand-dependent transcription factor GC-receptor (GR). GR function is exerted through DNA-binding-dependent and –independent mechanisms, classically referred to as transactivation (TA) and transrepression (TR). Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown. We evaluated skin wound healing in transgenic mice with keratinocyte-restricted expression of either wild type GR or a mutant GR that is TA-defective but efficient in TR (K5-GR and K5-GR-TR mice, respectively). Our data show that at days (d) 4 and 8 following wounding, healing in K5-GR mice was delayed relative to WT, with reduced recruitment of granulocytes and macrophages and diminished TNF-α and IL-1β expression. TGF-β1 and Kgf expression was repressed in K5-GR skin whereas TGF-β3 was up-regulated. The re-epithelialization rate was reduced in K5-GR relative to WT, as was formation of granulation tissue. In contrast, K5-GR-TR mice showed delays in healing at d4 but re-established the skin breach at d8 concomitant with decreased repression of pro-inflammatory cytokines and growth factors relative to K5-GR mice. Keratinocytes from both transgenic mice closed in vitro wounds slower relative to WT, consistent with the in vivo defects in cell migration. Overall, the delay in the early stages of wound healing in both transgenic models is similar to that elicited by systemic treatment with dexamethasone. Wound responses in the transgenic keratinocytes correlated with reduced ERK activity both in vivo and in vitro. We conclude that the TR function of GR is sufficient for negatively regulating early stages of wound closure, while TA by GR is required for delaying later stages of healing

Development of set of SNP markers for population genetics studies of lpe (Handroanthus sp.), a valuable tree genus from Latin America

A combination of restriction associated DNA sequencing (RADSeq) and low coverage MiSeq genome sequencing was used for the development of single nucleotide polymorphisms (SNP) and INDEL (insertion/deletions) genetic markers for Ipe (Handroanthus sp.). Of the 402 putative loci identified, 389 SNPs and INDELs (315 nuclear SPNs, six chloroplast INDELs, 15 chloroplast SNPs, 12 mitochondrial INDELs and 41 mitochondrial SNPs) were successfully genotyped at 93 individuals from Brazil, Bolivia and French Guiana using a MassARRAY® iPLEX™ platform. This set of markers will be invaluable for population genetics, phylogeography and DNA fingerprinting studie

Pollen morphology of Fridericia Mart. (Bignoniaceae) from Brazilian forest fragments

A pollen morphology study of 10 Brazilian native species of Fridericia (Bignoniaceae) from forest fragments was performed using light microscopy and scanning electron microscopy, in search of new characters that might increase knowledge of pollen morphology of the species, and also to help the taxonomic characterization of the genus. The pollen grains were acetolysed, measured, photographed, and described qualitatively. The quantitative data were analyzed by descriptive statistics and multivariate statistics. Non-acetolysed pollen grains were observed under scanning electron microscopy for further details of exine and pollen surface. The pollen grains are isopolar, medium to large, with circular to subcircular amb, oblate-spheroidal to subprolate, tricolporate, with long colpi, constricted or not, sometimes with margo, rounded or truncated at the polar ends, endoaperture lalongate, and microreticulate to reticulate exine, sexine thicker than nexine. The results indicate a stenopalynous genus, however, in some cases, it is possible to identify the studied species by the pollen morphology. Morphological considerations are also discussed.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Estadual Paulista, FCAV, Dept Biol Aplicada Agr, BR-14884900 Jaboticabal, SP, BrazilUniv Estadual Paulista, FCAV, Dept Biol Aplicada Agr, BR-14884900 Jaboticabal, SP, BrazilFAPESP: 12/09942-