title: Image-guided genomic analysis of tissue response to laser-induced thermal stress.
abstract: The cytoprotective response to thermal injury is characterized by transcriptional activation of "heat shock proteins" (hsp) and proinflammatory proteins. Expression of these proteins may predict cellular survival. Microarray analyses were performed to identify spatially distinct gene expression patterns responding to thermal injury. Laser injury zones were identified by expression of a transgene reporter comprised of the 70 kD hsp gene and the firefly luciferase coding sequence. Zones included the laser spot, the surrounding region where hsp70-luc expression was increased, and a region adjacent to the surrounding region. A total of 145 genes were up-regulated in the laser irradiated region, while 69 were up-regulated in the adjacent region. At 7 hours the chemokine Cxcl3 was the highest expressed gene in the laser spot (24 fold) and adjacent region (32 fold). Chemokines were the most common up-regulated genes identified. Microarray gene expression was successfully validated using qRT- polymerase chain reaction for selected genes of interest. The early response genes are likely involved in cytoprotection and initiation of the healing response. Their regulatory elements will benefit creating the next generation reporter mice and controlling expression of therapeutic proteins. The identified genes serve as drug development targets that may prevent acute tissue damage and accelerate healing.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Clark Center E-150, 318 Campus Drive, Stanford, California 94305-5427, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mackanos
authors.forename: Mike
authors.initials: M
authors.lastname: Helms
authors.forename: Flora
authors.initials: F
authors.lastname: Kalish
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D018869:Heat-Shock Response / Q000502:physiology*; D007834:Lasers; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence / Q000295:instrumentation*; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation*; D012879:Skin Physiological Phenomena / Q000528:radiation effects*; D018511:Systems Integration
chemical_list: D018840:HSP70 Heat-Shock Proteins