The Effects of Botulinum Toxin A on Collagen Synthesis, Expression of MMP (matrix metalloproteinases)-1,2,9 and TIMP (tissue inhibitors of metalloproteinase)-1 in the Keloid Fibroblasts

Abstract

Keloids are characterized by excessive extracelluar matrix (ECM) deposition such as collagen, fibronectin, elastin, and proteoglycans in the dermis. Recently, the use of botulinum toxin A (BTXA) in the treatment of keloids have had good results. To investigate the therapeutic effect of BTXA on the keloids, we evaluated the mRNA expression of collagen type I, type III, MMP (matrix metalloproteinases)-1, and TIMP (tissue inhibitor of metalloproteinases)-1 on keloid fibroblasts (KFs, n=5) after administration of BTXA. We also evaluated the enzymatic activity of MMP-2 and 9 by using zymography with BTXA. The same process was repeated after administration of TGF-beta in addition to BTXA. Type III collagen mRNA expression was decreased significantly when BTXA was administrated on KFs regardless of the presence or absence of TGF-beta. MMP-1 mRNA expression in KFs was increased according to the BTXA concentration increment, however, not increased with TGF-beta. Moreover, MMP-2 enzymatic activity in KFs was increased when BTXA administrated regardless of the presence or absence of TGF-beta. These results suggest that the down regulation of collagen III expression, the up regulation of MMP-1, and increased MMP-2 enzymatic activity on KFs after BTXA administration are able to decrease the excess collagen deposition in keloids.