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Hyaluronic acid production and CD44 expression in cultured dermal fibroblasts of patients with non-insulin-dependent diabetes mellitus with and without chronic ulcers on the lower extremity

Authors

  • Natalia Y. Yevdokimova PhD,

    Corresponding author
    1. From the Department of Molecular Immunology,
      * Natalia Y. Yevdokimova, PhD, Department of Molecular Immunology, Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovicha str., 01030 Kiev, Ukraine. Fax: +380 44 229 6365, Email: berezan@mathber.carrier.kiev.ua.
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  • Sergey E. Podpryatov MD, PhD

    1. Institute of Biochemistry, National Academy of Sciences of Ukraine, and Department of Surgery, First City Hospital, Ministry of Health of Ukraine, Kiev, Ukraine.
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* Natalia Y. Yevdokimova, PhD, Department of Molecular Immunology, Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovicha str., 01030 Kiev, Ukraine. Fax: +380 44 229 6365, Email: berezan@mathber.carrier.kiev.ua.

Abstract

It is well known that hyaluronic acid and its principal receptor, CD44, are implicated in the regulation of the tissue repair process, but their role in the formation of chronic diabetic ulcers has not been studied. Hyaluronic acid metabolism and CD44 expression are regulated by lactate, where their increased production is considered to affect the properties of fibroblasts in non-insulin-dependent diabetes mellitus. The aim of our work was to investigate the possible role of hyaluronic acid and CD44, and their regulation by lactate, in the abnormal wound healing of diabetes. Fibroblasts were derived from uninjured skin from four non-insulin-dependent diabetic patients with ulcers and four without ulcers; and from four healthy age-matched volunteers. We observed that diabetic fibroblasts of both groups produced more L-lactate (∼30%) and incorporated more 3H-glucosamine into the medium hyaluronic acid (∼28%) than controls. Fibroblasts of the diabetic group with ulcers, unlike those of the group without ulcers, showed significant increases in the high molecular weight hyaluronic acid accumulation in the pericellular matrix (30.5%, p < 0.01) and CD44 expression (27.0%, p < 0.05). Exogenous L-lactate dose-dependently, and equally for all fibroblasts lines, stimulated the accumulation of medium hyaluronic acid (3.7-fold) and CD44 expression (1.5-fold). However, fibroblasts from diabetic patients with ulcers were more (1.4-fold) sensitive to L-lactate in terms of CD44 expression, and responded to L-lactate by the increased accumulation of high molecular weight hyaluronic acid in the pericellular matrix (32.1%, p < 0.01). We propose that specific properties of fibroblasts from diabetic patients with ulcers may be involved in the increased susceptibility of these patients to chronic ulceration.

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