The Role of Focal Adhesion Kinase in Keratinocyte Fibrogenic Gene Expression

Autor: Sun Hyung Kwon, Zeshaan N. Maan, Geoffrey C. Gurtner, Michael Januszyk, Alexander J. Whittam, Jagannath Padmanabhan, Victor W. Wong, Melanie R. Major
Rok vydání: 2017
Předmět:
0301 basic medicine
Keratinocytes
focal adhesion kinase
keratinocyte
mechanotransduction
extracellular matrix
single-cell transcriptional analysis
skin fibrosis
hypertrophic scar
transcriptomics
Mechanotransduction
Cellular
Extracellular matrix
lcsh:Chemistry
0302 clinical medicine
Gene expression
Mechanotransduction
lcsh:QH301-705.5
Spectroscopy
Mice
Knockout
education.field_of_study
General Medicine
Computer Science Applications
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Keratinocyte
Signal Transduction
Population
Biology
Catalysis
Article
Inorganic Chemistry
Focal adhesion
03 medical and health sciences
Hypertrophic scar
Mediator
medicine
Animals
Humans
Physical and Theoretical Chemistry
education
Molecular Biology
Focal Adhesions
Organic Chemistry
medicine.disease
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Focal Adhesion Protein-Tyrosine Kinases
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 18, Iss 9, p 1915 (2017)
International Journal of Molecular Sciences; Volume 18; Issue 9; Pages: 1915
ISSN: 1422-0067
Popis: Abnormal skin scarring causes functional impairment, psychological stress, and high socioeconomic cost. Evidence shows that altered mechanotransduction pathways have been linked to both inflammation and fibrosis, and that focal adhesion kinase (FAK) is a key mediator of these processes. We investigated the importance of keratinocyte FAK at the single cell level in key fibrogenic pathways critical for scar formation. Keratinocytes were isolated from wildtype and keratinocyte-specific FAK-deleted mice, cultured, and sorted into single cells. Keratinocytes were evaluated using a microfluidic-based platform for high-resolution transcriptional analysis. Partitive clustering, gene enrichment analysis, and network modeling were applied to characterize the significance of FAK on regulating keratinocyte subpopulations and fibrogenic pathways important for scar formation. Considerable transcriptional heterogeneity was observed within the keratinocyte populations. FAK-deleted keratinocytes demonstrated increased expression of genes integral to mechanotransduction and extracellular matrix production, including Igtbl, Mmpla, and Col4a1. Transcriptional activities upon FAK deletion were not identical across all single keratinocytes, resulting in higher frequency of a minor subpopulation characterized by a matrix-remodeling profile compared to wildtype keratinocyte population. The importance of keratinocyte FAK signaling gene expression was revealed. A minor subpopulation of keratinocytes characterized by a matrix-modulating profile may be a keratinocyte subset important for mechanotransduction and scar formation.
Databáze: OpenAIRE
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