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LL‐37 regulates the overexpression of vascular endothelial growth factor (VEGF) and c‐IAP‐2 in human keratinocytes
Author(s) -
RodríguezMartínez Sandra,
CancinoDiaz Juan Carlos,
VargasZuñiga Luis Martin,
CancinoDiaz Mario Eugenio
Publication year - 2008
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/j.1365-4632.2008.03340.x
Subject(s) - hacat , transfection , microbiology and biotechnology , vascular endothelial growth factor , messenger rna , downregulation and upregulation , vascular endothelial growth factor a , biology , keratinocyte , cancer research , biochemistry , in vitro , gene , vegf receptors
Background The antimicrobial peptide PR39 is a porcine cathelicidin with angiogenic and antiapoptotic activities, as it can regulate the expression of vascular endothelial growth factor (VEGF) and inhibitor apoptosis protein‐2 (c‐IAP‐2) in endothelial cells. The human homolog LL‐37 has been found to be highly expressed in human keratinocytes from psoriatic patients, but it is not known whether LL‐37 can modulate the expression of VEGF and c‐IAP‐2 in keratinocytes, as both molecules are involved in the overgrowth of psoriatic skin. Therefore, in this work, we studied the possible role of CAP18/LL‐37 in the modulation of VEGF and c‐IAP‐2 expression in human keratinocytes. Methods The CAP18/LL‐37 gene was cloned into a plasmid that contained green fluorescent protein (GFP). This plasmid was called pGFP‐CAP18/LL‐37. The expression of LL‐37, VEGF, and c‐IAP‐2 was determined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blotting in HaCaT cells transfected with pGFP‐CAP18/LL‐37. Specific DNAzymes were used to break the CAP18/LL‐37 mRNA (DNAz‐CAP18/LL‐37). Results HaCaT cells transfected with pGFP‐CAP18/LL‐37 showed the upregulation of VEGF and c‐IAP‐2 mRNAs. Hypoxia‐inducible factor‐1α (HIF‐1α) mRNA expression did not change during the assays; however, its protein was increased, as well as the VEGF protein. HaCaT cells cotransfected with pGFP‐CAP18/LL‐37 and DNAz‐CAP18/LL‐37 showed depleted expression of LL‐37, VEGF, and c‐IAP‐2 mRNAs. Conclusions These results suggest that LL‐37 may modulate the expression of VEGF and c‐IAP‐2 via HIF‐1α in human keratinocytes.