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Targeting of Sp1 transcription factor: a novel therapeutic approach for Keloids, an in vitro analysis
Author(s) -
Mukhopadhyay A.,
Khoo A.,
Cheong H. H.,
Chan S. Y.,
Aalami O.,
Lim I. J.,
Phan T. T.
Publication year - 2007
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2007.00627.x
Subject(s) - keloid , extracellular matrix , cancer research , sp1 transcription factor , in vitro , chemistry , transcription factor , scars , microbiology and biotechnology , promoter , medicine , biology , pathology , gene expression , biochemistry , gene
Keloid scars are fibroproliferative disorders characterized by the accumulation of extracellular matrix (ECM) components resulting in a fibrotic condition. Several ECM promoters are regulated by Sp1. Thus, our aim was to investigate the role of Sp1 in keloid pathogenesis and investigate the antiproliferative and antifibrotic effects of Wp631 and mitoxantrone, potent inhibitors of Sp1‐activated transcription. An elevated level of Sp1 was observed in tissue extracts obtained from keloid tissue. Serum stimulation elevated Sp1 levels in keloid fibroblasts (KF). Under coculture conditions Sp1 seemed to be downregulated. Wp631 and mitoxanthrone in serum growth factors resulted in a reduced expression of ECM components in KF. Both Wp631 and mitoxanthrone were also able to inhibit the proliferation of normal and keloid keratinocytes and fibroblasts significantly. As Wp631 seems to be potent in downregulating the ECM components in KF and also inhibiting the proliferation of these cells it could be explored as a possible therapeutic agent in the treatment of keloids.