A new selective vascular endothelial growth factor receptor 2 inhibitor ablates disease in a mouse model of psoriasis

Abstract

Psoriasis is a common chronic inflammatory skin disease and its underlying pathogenesis is still not fully understood. Therapeutic interventions are currently limited and restricted to the treatment of symptoms rather than targeting the mechanisms underlying the disease. Vascular remodeling is a hallmark of psoriasis; however, anti-vascular strategies to treat psoriasis have received little attention to date, particularly systemic treatment with a small molecule compound. The aim of this study was to investigate the anti-inflammatory effect of a newly identified vascular endothelial growth factor (VEGF) receptor 2 inhibitor, SKLB1002, and its possible mechanism of action in a transgenic mouse model of psoriasis. Fifteen 8-12-week‑old K14-VEGF transgenic mice received consecutive intraperitoneal (i.p.) injections of SKLB1002, vehicle or saline for 4 weeks. After 4 weeks of treatment, the disease symptoms were assessed and histological analyses were performed on ear sections by hematoxylin and eosin (HE) and immunohistochemistry staining. Systemic treatment with SKLB1002 reduced symptoms of ear inflammation in K14/VEGF transgenic mice, the pathological score was significantly decreased, and acanthosis, focal parakeratosis, hyperkeratosis and hemangiectasis were improved. Furthermore, systemic treatment with SKLB1002 significantly reduced vascular abnormalities, permeability and T-cell infiltration. These results demonstrated that targeted inhibition of VEGFR2 by a small molecule inhibitor is an effective method, which may be a new therapeutic option for psoriasis therapy.

Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice

“…The sections were deparaffinized before staining. To demonstrate morphologic changes and eosinophil infiltration, sections were stained with hematoxylin (Merck, Darmstadt, Germany) and 1 % eosin (Sigma-Aldrich Co.) [ 21 ]. Staining with toluidine blue (Merck) was performed for mast cell detection.…”

Possible role of mast cells and IL-37 in the pathogenesis of psoriasis

“…VEGF is generated in response to soluble mediators, such as cytokines, and its major receptor kinaseinsert-domain-containing receptor (KDR) which has a selective mitogenic effect on endothelial cells (43). It has been found that the epidermal over-expression of VEGF in transgenic mice, stimulated by inflammatory cytokines, leads to a phenotype nearly identical to that of PsA (44). VEGF stimulation with cytokines is therefore involved in PsA pathogenesis and several different VEGF polymorphisms are associated with an increased risk of developing PsA.…”

Anti-inflammatorische Wirkung des inositoylierten Plättchen-aktivierenden Faktors (Ino-C2-PAF) in vitro und in vivo

“…In einer 2009 erschienen Publikation kam es unter anti-angiogener Therapie eines kolorektalen Karzinoms mit Bevacizumab, einem Antikörper gegen VEGF, auch zur Abheilung einer vorbestehenden Psoriasis (Akman et al 2009). Der therapeutische Effekt anti-angiogener Therapien konnte auch in verschiedenen Mausmodellen psoriasiformer Entzündungen belegt werden (Diaconu et al 2013;Yan et al 2013;Zibert et al 2011;Schönthaler et al 2009).…”