Pigment epithelium‐derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars

Abstract

Scar forming wounds are often characterized by higher levels of vascularity than non‐scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause‐effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full‐thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post‐wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF‐A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium‐derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post‐wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF‐335). rPEDF and PEDF‐335 were administered intradermally from day 4 post‐wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF‐335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF‐335, as a potential new strategy for the prevention or treatment of HSs.

In vitro modeling of solid tumor interactions with perfused blood vessels

“…6) 4 . Specifically, our reverse western blot array and cell migration data revealed that the combination of VEGF, HB-EGF, and PIGF-all of which are secreted by HLFs-work together to establish a pro-angiogenic cell culture environment, unlike MSCs, which are known as anti-inflammatory cell types secreting numerous anti-angiogenic factors, such as TIMP-1, PEDF, and TSP-1 [26][27][28][29][30][31][32] . Further research is required to identify the molecular mechanisms by which these four factors cooperatively promote angiogenesis and to develop the next generation of anti-angiogenic cancer therapeutics.…”

Study on the Bidirectional Regulation of Skin Regeneration by Tension

“…Reducing tension can not only promote the growth of immune cells, but also promote the regeneration of blood vessels, tissue regeneration accelerates and can also reduce scar formation. Hyperplastic scar is pathological scar caused by excessive synthesis and deposition of collagen [15]. Skin mechanical tension can cause fibroblast proliferation and transformation through various mechanisms, regulate protein excretion, inhibit apoptosis, induce pathological scar formation, and promote its proliferation and expansion.…”

Anatomical Anal Stenosis after PPH: Insights from a Retrospective Study and Rat Model

“…Meanwhile, there is existing evidence indicating that excessive angiogenic response has been suggested to promote scar formation [ 59 ]. The involvement of angiogenesis in scar formation has been demonstrated in various models, including hypertrophic scars, traumatic brain injury, and myocardial infarction [ 60 , 61 , 62 ]. The promotion of angiogenesis has been shown to enhance scar formation in specific contexts, such as skin scarring and spinal cord injury [ 63 , 64 ].…”