Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.
The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCα-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCα-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCα-/- wounds. Thus, our data reveal a previously unappreciated role for PKCα in the regulation of ECM structure and deposition during skin wound healing.
The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK; Institute of Medical Biology, Epithelial Epigenetics Laboratory, Agency for Science, Technology and Research, Singapore, Singapore.
Nichola H
NH
Cooper
The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK.
Jeya P
JP
Balachandra
The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK. Electronic address: matthew.j.hardman@manchester.ac.uk.
Matthew J
MJ
Hardman
D000818:Animals; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006097:Granulation Tissue / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051571:Protein Kinase C-alpha / Q000235:genetics*; D011509:Proteoglycans / Q000502:physiology; D013718:Tensile Strength; D014945:Wound Healing
D011509:Proteoglycans; D003094:Collagen; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha