Octanoyl esterification of low molecular weight sulfated galactan enhances the cellular uptake and collagen expression in fibroblast cells

Waraporn Sakaew; Somsuda Somintara; Kamonwan Jongsomchai; Jamal El-Abid; Kanokpan Wongprasert; José Kovensky; Tawut Rudtanatip

doi:10.3892/br.2023.1681

Octanoyl esterification of low molecular weight sulfated galactan enhances the cellular uptake and collagen expression in fibroblast cells

Biomed Rep. 2023 Oct 23;19(6):99. doi: 10.3892/br.2023.1681. eCollection 2023 Dec.

Authors

Waraporn Sakaew¹, Somsuda Somintara¹, Kamonwan Jongsomchai², Jamal El-Abid³, Kanokpan Wongprasert⁴, José Kovensky⁵, Tawut Rudtanatip¹

Affiliations

¹ Electron Microscopy Unit, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
² Division of Anatomy, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
³ Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm 10691, Sweden.
⁴ Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
⁵ Laboratory of Glycochemistry and Agroresources UR 7378, Picardie Institute of Chemistry FR 3085, University of Picardie Jules Verne, 80000 Amiens, France.

Abstract

Low molecular weight sulfated galactan (LMSG) supplemented with octanoyl ester (Oct-LMSG) demonstrated superior wound healing activity compared to the unsupplemented LMSG in a fibroblast wound model. To test the hypothesis that the increased bioactivity of Oct-LMSG may depend on its penetration into the plasma membrane, its cellular uptake was investigated and collagen production in fibroblast cells was assessed for the first time. The cellular uptake of Oct-LMSG was examined using indirect immunofluorescence and a confocal laser scanning microscope. In addition, the degree of fibroblast activation associated with this uptake was evaluated. The results indicated increased LMSG internalization in fibroblasts treated with Oct-LMSG. Transmission electron micrographs revealed the ultrastructure of active protein production in fibroblasts upon treatment with Oct-LMSG. In addition, Oct-LMSG upregulated the expression of type I collagen mRNA and proteins, as well as related signaling molecules involved in collagen synthesis, including collagen type I α1 chain (Col1A1), Col1A2, phosphorylated (p)-Smad2/3 and p-Smad4. The current findings support the notion that the supplementation of LMSG with octanoyl enhanced its cellular uptake into fibroblasts and, as a result, regulated the expression of type I collagen in fibroblasts via the activation of the Smad signaling pathway. This study demonstrates the therapeutic potential of Oct-LMSG in promoting tissue regeneration.

Keywords: Smad proteins; collagen-I; fibroblasts; low molecular weight sulfated galactan; octanoyl ester.

Grants and funding

Funding: This work was financially supported by the Office of the Permanent Secretary at the Ministry of Higher Education, Science, Research and Innovation and the Thailand Science Research and Innovation (grant no. RGNS 64-044), the National Research Council of Thailand (NRCT; grant no. N42A650206) and the Khon Kaen University Faculty of Medicine Invitation Research fund (grant no. IN66028).