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The results suggest that modulation of PEDF levels may play a pivotal role in skin homoeostasis and the response of keratinocytes to injury or inflammatory insults. Pigment epithelium-derived factor (Serpinf1) is a 50-kDa secreted glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF has been demonstrated to be one of the most potent endogenously buy CHIR-99021 produced physiological and pathological anti-angiogenic factors [1, 2] and also has direct and indirect suppressive effect on tumor growth [3]. PEDF has been detected in multiple tissues including brain, spinal cord, liver, bone, eye, heart, lung and plasma [4]. PEDF expression has also been reported in the dermal and epidermal layers of skin. Alterations in the levels of PEDF have been implicated in skin ageing and the pathogenesis of some skin conditions, Selleck Y27632 including melanoma, psoriasis and condyloma acuminatum [5-8]. Given its functions and wide pattern of expression, PEDF has been proposed to be a factor that promotes the return to tissue homoeostasis following pathologic insult [9]. Evidence for such function has been described in the horse, a species in which PEDF levels have been shown to undergo modulation in skin wounds [10]. During wound healing, keratinocytes proliferate and migrate across the wound bed, contributing to wound closure; these cells act upon and respond to signals from the underlying vascularized dermis. While it is likely that PEDF plays a role in the regulation of angiogenesis that is critical to skin homoeostasis and recovery from injury, it is unknown whether secreted PEDF participates in the dynamic reciprocity between Fleroxacin epidermal and dermal layers. Therefore, we examined the regulation of PEDF expression in keratinocytes under in vitro conditions that mimic those of a skin wound. The data demonstrate that PEDF expression in primary isolated skin keratinocytes is modulated by injury stimuli, including a mechanical disruption and inflammatory cytokines. Our results suggest a role for PEDF in modulating not only angiogenesis, but also keratinocyte function following tissue injury. Effects injury-related stimuli on PEDF expression in human skin keratinocytes in vitro; effects of PEDF on keratinocyte adhesion, migration and proliferation in vitro. See supplemental materials. From our existing microarray database [11], the relative gene expression of PEDF in mouse skin wounds was significantly decreased at 12-h postwounding when compared to uninjured skin (8.9 vs 10.7, P?
