title: A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing.
abstract: Chronic or non-healing wounds are a major concern in clinical practice and these wounds are mostly associated with diabetes, and venous and pressure ulcers. Wound healing is a complex process involving overlapping phases and the primary phase in this complex cascade is the inflammatory state. While inflammation is necessary for wound healing, a prolonged inflammatory phase leads to impaired healing. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that are expressed in high levels under stress conditions. Recently, we demonstrated that a deficiency in CIRP led to decreased inflammation and mortality in an experimental model of hemorrhagic shock. Thus, we hypothesized that a deficiency in CIRP would accelerate the inflammatory phase and lead to an improvement in cutaneous wound healing. In this study, to examine this hypothesis, a full-thickness wound was created on the dorsum of wild-type (WT) and CIRP-/- mice. The wound size was measured every other day for 14 days. The wound area was significantly decreased in the CIRP-/- mice by day 9 and continued to decrease until day 14 compared to the WT mice. In a separate cohort, mice were sacrificed on days 3 and 7 after wounding and the skin tissues were harvested for histological analysis and RNA measurements. On day 3, the mRNA expression of tumor necrossis factor (TNF)-α in the skin tissues was increased by 16-fold in the WT mice, whereas these levels were increased by 65-fold in the CIRP-/- mice. Of note on day 7, while the levels of TNF-α remained high in the WT mice, these levels were significantly decreased in the CIRP-/- mice. The histological analysis of the wounded skin tissue indicated an improvement as early as day 3 in the CIRP-/- mice, whereas in the WT mice, infiltrated immune cells were still present on day 7. On day 7 in the CIRP-/- mice, Gr-1 expression was low and CD31 expression was high, whereas in the WT mice, Gr-1 expression was high and CD31 expression was low, indicating that the CIRP-/- mice have already moved into the angiogenesis and tissue formation phase, whereas the WT mice were still in the inflammatory state. These data collectively suggest that a deficiency in CIRP accelerates the wound healing process.
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Idrovo
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Weng Lang
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Hao Ting
authors.initials: HT
authors.lastname: Yen
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nicastro
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Gene F
authors.initials: GF
authors.lastname: Coppa
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000235:genetics*
chemical_list: C106176:Cirbp protein, mouse; D016601:RNA-Binding Proteins