Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression.
10.1007/s13770-016-0017-y
- Author:
Hyunju PARK
1
;
Eunjin AN
;
Ae Ri Cho LEE
Author Information
1. College of Pharmacy, Duksung Women's University, 33 Samyang-ro144-gil, Dobong-gu, Seoul 01369, Korea. aeri@ds.ac.kr
- Publication Type:Original Article
- Keywords:
KTTKS;
Myofibroblast;
α-SMA;
CTGF;
Scar
- MeSH:
Actins*;
Blotting, Western;
Cell Culture Techniques;
Cicatrix;
Collagen;
Connective Tissue Growth Factor*;
Connective Tissue*;
Fibroblasts;
Fluorescent Antibody Technique;
Microscopy, Confocal;
Myofibroblasts;
Stress Fibers;
Wound Healing;
Wounds and Injuries*
- From:
Tissue Engineering and Regenerative Medicine
2017;14(1):73-80
- CountryRepublic of Korea
- Language:English
-
Abstract:
To evaluate whether Palmitoyl-pentapeptide (Pal-KTTKS), a lipidated subfragment of type 1 pro-collagen (residues 212–216), plays a role in fibroblast contractility, the effect of Pal-KTTKS on the expression of pro-fibrotic mediators in hypertropic scarring were investigated in relation with trans-differentiation of fibroblast to myofibroblast, an icon of scar formation. α-SMA was visualized by immunofluorescence confocal microscopy with a Cy-3-conjugated monoclonal antibody. The extent of α-SMA-positive fibroblasts was determined in collagen lattices and in cell culture study. Pal-KTTKS (0–0.5 µM) induced CTGF and α-SMA protein levels were determined by western blot analysis and fibroblast contractility was assessed in three-dimensional collagen lattice contraction assay. In confocal analysis, fibroblasts were observed as elongated and spindle shapes while myofibroblast observed as squamous, enlarged cells with pronounced stress fibers. Without Pal-KTTKS treatment, three quarters of the fibroblasts differentiates into the myofibroblast; α-SMA-positive stress fibers per field decreased twofold with 0.1 µM Pal-KTTKS treatment (75 ± 7.1 vs 38.6 ± 16.1%, n = 3, p<0.05). The inhibitory effect was not significant in 0.5 µM Pal-KTTKS treatment. Stress fiber level and collagen contractility correlates with α-SMA expression level. In conclusion, Pal-KTTKS (0.1 µM) reduces α-SMA expression and trans-differentiation of fibroblasts to myofibroblast. The degree of reduction is dose-dependent. An abundance of myofibroblast and fibrotic scarring is correlated with excessive levels of α-SMA and collagen contractility. Delicate balance between the wound healing properties and pro-fibrotic abilities of pentapeptide KTTKS should be considered for selecting therapeutic dose for scar prevention.
