Genome-wide expression analysis of wounded skin reveals novel genes involved in angiogenesis
- 404 Downloads
Wound healing is a multistage process involving collaborative efforts of different cell types and distinct cellular functions. Among others, the high metabolic activity at the wound site requires the formation and sprouting of new blood vessels (angiogenesis) to ensure an adequate supply of oxygen and nutrients for a successful healing process. Thus, a cutaneous wound healing model was established to identify new factors that are involved in vascular formation and remodeling in human skin after embryonic development. By analyzing global gene expression of skin biopsies obtained from wounded and unwounded skin, we identified a small set of genes that were highly significant differentially regulated in the course of wound healing. To initially investigate whether these genes might be involved in angiogenesis, we performed siRNA experiments and analyzed the knockdown phenotypes using a scratch wound assay which mimics cell migration and proliferation in vitro. The results revealed that a subset of these genes influence cell migration and proliferation in primary human endothelial cells (EC). Furthermore, histological analyses of skin biopsies showed that two of these genes, ALBIM2 and TMEM121, are colocalized with CD31, a well known EC marker. Taken together, we identified new genes involved in endothelial cell biology, which might be relevant to develop therapeutics not only for impaired wound healing but also for chronic inflammatory disorders and/or cardiovascular diseases.
KeywordsAngiogenesis Genome-wide expression analyses Human skin Wound healing
We thank Sonja Wessel, Boris Kristof, and Thomas Lange for helpful discussions and support concerning capillary microscopy and analyses.
Conflict of interest
All authors were employees at Beiersdorf at the time point of the study. B. Brückner received consultation fees from Beiersdorf.
- 12.Freinkel RK (2001) The biology of the skin. Parthenon Publishing Group, New YorkGoogle Scholar
- 13.Mendonca RJ (2012) Angiogenesis in wound healing. Tissue regeneration—from basic biology to clinical applicationGoogle Scholar
- 15.DiPietro LA (2013) Angiogenesis and scar formation in healing wounds. Curr Opin Rheumatol 25(1):87–91Google Scholar
- 16.Gronniger E et al (2010) Aging and chronic sun exposure cause distinct epigenetic changes in human skin. PLoS Genet 6(5):e1000971Google Scholar
- 18.Bronneke S et al (2012) DNA methylation regulates lineage-specifying genes in primary lymphatic and blood endothelial cells. Angiogenesis 15(2):317–329Google Scholar
- 21.Kanitakis J (2002) Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol 12(4):390–399; quiz 400–401Google Scholar
- 22.Fritsch P (2004) Aufbau und Funktionen der Haut. In: Dermatologie und Venerologie. Springer, Berlin. 2. AuflageGoogle Scholar
- 32.Chen L et al (2010) Positional differences in the wound transcriptome of skin and oral mucosa. BMC Genomics 11:471Google Scholar