Expression of galectin‑7 in vulvar lichen sclerosus and its effect on dermal fibroblasts

Abstract

Lichen sclerosus is a chronic and inflammatory disease. Extensive studies have focused on the epidermis, with the dermis or epidermis-dermis receiving less attention. To investigate the role of galectin-7, a keratinocyte protein, in vulvar lichen sclerosus (VLS) and its potential effects on dermal fibroblasts, immunohistochemical staining was performed with VLS tissue samples and normal control samples. The expression of galectin-7 was determined by evaluating the galectin-7 integrated density analysis, and further assessed by western blot analysis. Dermal fibroblasts were isolated from the normal tissue of the female anogenital region following sexual plastic surgery. A cell viability assay was performed on isolated dermal fibroblast cells in the presence or absence of galectin-7. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the transcriptional level of collagen I and collagen III in the response to different doses of galectin-7. In the immunohistochemical analysis, galectin-7 demonstrated a significantly elevated level in VLS, compared to control tissues, which was confirmed by western blot analysis. In the analysis of primary dermal fibroblast cells, galectin-7 significantly inhibited the viability rate of fibroblasts in a dose-dependent manner. RT-qPCR data revealed that the transcription level of collagen I and collagen III were positively associated with the galectin-7 treatment concentration. The overexpression of galectin-7 is associated with the progression of VLS in the epidermis, a high concentration of galectin-7 inhibits the viability of the primary vulvar dermal fibroblasts, and stimulates the accumulation of collagen I and collagen III in dermal fibroblast cultures, thus galectin-7 may serve as a drug target during VLS progression.

<p>Vulvar Lichen Sclerosus: Current Perspectives</p>

“…24,25 Sclerotic tissue formation is also facilitated by dysregulation involving a keratinocyte protein regulated by p53 called galectin-7, which inhibits fibroblast growth and increases collagen synthesis. 26 The inflammation of the T h 1 cytokine environment leads to the release of reactive oxygen species (ROS), promoting autoimmunity and oxidative stress. 12 Oxidative stress contributes to inactivation of tumor suppressor genes involving p53 and CDKN2A, leading to cell proliferation and transformation to malignancy.…”

Lichen Sclerosus: An autoimmunopathogenic and genomic enigma with emerging genetic and immune targets

“…The cellular activity of fibroblasts in LS was further investigated with the regulatory role of galectin-7, a keratinocyte protein under p53 regulation [79]. Zhao et al [80] noted high galectin-7 expression levels in LS tissue that may exert a dual effect on dermal fibroblasts by (1) inhibiting growth and (2) promoting the transcription of type I and type III collagen, both primary collagen types seen to be overly expressed in LS (Figure 3). Even though galectin-7 expression was localized only to the epidermis of LS tissue, it is possible that galectin-7 may find its way via paracrine signaling from keratinized epithelial cells that originally synthesized galectin-7 in the epidermis, to a surface receptor of dermal fibroblast in the dermis in order to downregulate fibroblast growth and increase collagen I & III transcription [80].…”

Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects

“…Further potential actors of these histopathological changes are collagen V (COLV) and galectin-7 which both appear increased in VLS [84,85]. Increased COLV expression, and contextual ECM1 decrease, may contribute to both the disappearance of elastic fibres in the upper homogenized dermis and the abnormal collagen metabolism.…”