The tetrapeptide acetyl‐serine‐aspartyl‐lysine‐proline improves skin flap survival and accelerates wound healing

Abstract

The tetrapeptide acetyl-serine-aspartyl-lysine-proline (AcSDKP) has recently been recognized as a potent angiogenic factor. Given the importance of vascular blood supply in the process of tissue repair we have investigated the ability of AcSDKP to contribute to the repair of cutaneous injuries by using dorsal and abdominal skin flap models. Postoperative subdermal AcSDKP injections (5 microg/kg/injection twice a day for 3 days following flap elevation) prevented marginally perfused areas from undergoing necrosis. Mean skin survival area of abdominal and dorsal flaps ranged, respectively, from 50.9+/-19.3 and 53.4+/-4.2% in the control groups to 66.4+/-7.5 and 74.7+/-6.6% in AcSDKP-treated groups. Furthermore, in an ex vivo assay, AcSDKP applied locally to skin explants at doses from 10(-8) to 10(-5) M improved survival of the explanted skin exposed to UVB irradiation at 10 J/cm2. Increased reepithelialization, as well as higher levels of expression of basal keratin 14 and increased expression of fibronectin was observed after topical application of AcSDKP. These data provide experimental evidence that AcSDKP can improve the viability of ischemic skin flaps in the rat by promoting angiogenesis. Moreover, it enhances wound healing of injured avascular skin explants. Thus, these findings identify AcSDKP as a new tissue-repair agent and suggest its potential clinical use for the management of skin wounds.

N-acetyl-seryl-aspartyl-lysyl-proline: a valuable endogenous anti-fibrotic peptide for combating kidney fibrosis in diabetes

“…AcSDKP reportedly exhibits anti-fibrotic organ-protective effects in various experimental models (Fromes et al, 2006; Omata et al, 2006; Castoldi et al, 2013; Zuo et al, 2013). Additionally, we have reported that AcSDKP prevents mesangial matrix expansion in diabetic db/db mice (Shibuya et al, 2005).…”

“…AcSDKP (Liu et al, 2003; Wang et al, 2004; Fromes et al, 2006) and its precursor peptide, Tβ4 (Malinda et al, 1997; Huff et al, 2001; Koutrafouri et al, 2001; Philp et al, 2003) have been shown to enhance angiogenesis and exhibit anti-fibrotic effects associated with normalization of organ function (Smart et al, 2007). AcSDKP improves skin flap survival and accelerates wound healing (Fromes et al, 2006).…”

“…AcSDKP (Liu et al, 2003; Wang et al, 2004; Fromes et al, 2006) and its precursor peptide, Tβ4 (Malinda et al, 1997; Huff et al, 2001; Koutrafouri et al, 2001; Philp et al, 2003) have been shown to enhance angiogenesis and exhibit anti-fibrotic effects associated with normalization of organ function (Smart et al, 2007). AcSDKP improves skin flap survival and accelerates wound healing (Fromes et al, 2006). The association between tumor angiogenesis and the levels of Tβ4 and AcSDKP has been studied by Wdzieczak-Bakala et al (1990), and these authors have proposed that high levels of Tβ4 and AcSDKP are linked to tumor progression in hematologic malignancies (Liu et al, 2006, 2008, 2009a, 2010).…”

The Blood is Rich in Different Types of Mesoderm Derived Stem and Progenitor Cells

“…The view that many pathological conditions could benefi t from the inhibition or stimulation of vasculogenesis and angiogenesis was supported by multiple investigations [63][64][65]. However, some apparently contradictory fi ndings have marked EPC research.…”

AcSDKP: a new potential marker of malignancy of the thyroid gland

“…AcSDKP prevents primitive hematopoietic cells entry into S-phase of a cell cycle [11,12]. The recent studies revealed that AcSDKP induces angiogenesis and improves wound healing, as well as heart regeneration after ischemia [13][14][15]. The significant increase of serum levels of tetrapeptide was observed in patients with leukemia [16].…”