Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin.
10.1007/s13238-015-0198-5
- Author:
Chunji QUAN
1
;
Moon Kyun CHO
2
;
Yuan SHAO
3
;
Laurel E MIANECKI
4
;
Eric LIAO
4
;
Daniel PERRY
4
;
Taihao QUAN
5
Author Information
1. Department of Pathology, Affiliated Hospital of Yanbian University, Yanji, 133000, China.
2. Department of Dermatology, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
3. Hollings Cancer Center Biorepository and Tissue Analysis Resource, Medical University of South Carolina, Charleston, SC, 29425, USA.
4. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
5. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. thquan@umich.edu.
- Publication Type:Journal Article
- Keywords:
SDF-1;
dermal fibroblast;
keratinocyte;
proliferation;
psoriasis;
skin cancer
- MeSH:
Adult;
Cell Proliferation;
Chemokine CXCL12;
genetics;
Epidermal Cells;
Epidermis;
pathology;
Extracellular Signal-Regulated MAP Kinases;
metabolism;
Fibroblasts;
metabolism;
Gene Expression Regulation;
Humans;
Keratinocytes;
cytology;
pathology;
Signal Transduction;
Skin Diseases;
genetics;
pathology
- From:
Protein & Cell
2015;6(12):890-903
- CountryChina
- Language:English
-
Abstract:
Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real-time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in normal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermal keratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by interfering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.
