Upregulated stromal cell-derived factor 1 (SDF-1) expression and its interaction with CXCR4 contribute to the pathogenesis of severe pterygia.

Abstract

PURPOSE:

Stromal cell-derived factor 1 (SDF-1) and its interaction with chemokine receptor 4 (CXCR4) have been noted for participating in the wound healing process, and may paradoxically develop hypertrophic scarring. With viewing pterygia as a product of exaggerated wound formation, we evaluated the effects of SDF-1 and CXCR4 on determining the severity of pterygia.

METHODS:

Human pterygial fibroblasts were cultured from excised tissues. Then, expression levels of SDF-1 and CXCR4 were assessed at both the mRNA and protein levels and analyzed with respect to the severity (grade T1 to T3) of pterygia. Expression patterns of SDF-1 and CXCR4 in pterygium tissues were evaluated by immunohistochemistry. Additionally, to investigate the SDF-1-induced myofibroblast transformation of pterygial fibroblasts, the correlation between SDF-1 and α-smooth muscle actin (α-SMA) expression levels was evaluated. Furthermore, α-SMA levels in pterygial fibroblasts were determined before and after knockdown of SDF-1 and blockade of CXCR4 by AMD3100.

RESULTS:

Stromal cell-derived factor 1 and CXCR4 were expressed in identical areas in severe pterygium tissues (grade T3) and CXCR4-immunopositive cells were concentrated at perivascular regions. Stromal cell-derived factor 1 levels in cultured pterygial fibroblasts correlated positively with the severity of pterygia. Stromal cell-derived factor 1 levels had a significant, positive correlation with α-SMA levels in pterygial fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF-1/CXCR4 signaling in severe pterygia significantly reduced α-SMA levels.

CONCLUSIONS:

Stromal cell-derived factor 1 expression is upregulated in severe pterygia, and SDF-1 and CXCR4 interaction may contribute to the myofibroblast transformation, which can be possibly restored through the downregulation of the SDF-1/CXCR4 axis.

• Authors: Kyoung Woo Kim, Soo Hyun Park, Seung Hoon Lee, Jae Chan Kim
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 54 Issue 12 Pg. 7198-206 (Nov 01 2013) ISSN: 1552-5783 [Electronic] United States
• PMID: 24114538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ACTA2 protein, human
• Actins
• Benzylamines
• CXCR4 protein, human
• Chemokine CXCL12
• Cyclams
• Heterocyclic Compounds
• RNA, Messenger
• Receptors, CXCR4
• plerixafor

Topics

• Actins (metabolism)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Benzylamines
• Blotting, Western
• Cell Differentiation (drug effects)
• Cells, Cultured
• Chemokine CXCL12 (genetics, metabolism)
• Cyclams
• Female
• Fibroblasts (metabolism)
• Heterocyclic Compounds (pharmacology)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Myofibroblasts (drug effects)
• Prospective Studies
• Pterygium (etiology)
• RNA, Messenger (metabolism)
• Receptors, CXCR4 (antagonists & inhibitors, genetics, metabolism)
• Up-Regulation
• Young Adult