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      Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression

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      , ,
      Tissue Engineering and Regenerative Medicine
      Springer Singapore
      KTTKS, Myofibroblast, α-SMA, CTGF, Scar

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          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.

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          Author and article information

          Contributors
          +82-2-901-8388 , aeri@ds.ac.kr
          Journal
          Tissue Eng Regen Med
          Tissue Eng Regen Med
          Tissue Engineering and Regenerative Medicine
          Springer Singapore (Singapore )
          1738-2696
          2212-5469
          19 January 2017
          February 2017
          : 14
          : 1
          : 73-80
          Affiliations
          ISNI 0000 0004 0532 6173, GRID grid.410884.1, College of Pharmacy, , Duksung Women’s University, ; 33 Samyang-ro144-gil, Dobong-gu, Seoul, 01369 Korea
          Article
          PMC6171572 PMC6171572 6171572 17
          10.1007/s13770-016-0017-y
          6171572
          30603464
          6cd674e1-3426-48d2-b978-809e273366b7
          © The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht 2017
          History
          : 2 November 2016
          : 24 November 2016
          : 11 December 2016
          Categories
          Original Article
          Custom metadata
          © The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht 2017

          Myofibroblast,KTTKS,α-SMA,Scar,CTGF
          Myofibroblast, KTTKS, α-SMA, Scar, CTGF

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