A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing

  • Authors:
    • Juan Pablo Idrovo
    • Asha Jacob
    • Weng Lang Yang
    • Zhimin Wang
    • Hao Ting Yen
    • Jeffrey Nicastro
    • Gene F. Coppa
    • Ping Wang
  • View Affiliations

  • Published online on: January 7, 2016     https://doi.org/10.3892/ijmm.2016.2451
  • Pages: 423-428
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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.

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February 2016
Volume 37 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
APA
Idrovo, J.P., Jacob, A., Yang, W.L., Wang, Z., Yen, H.T., Nicastro, J. ... Wang, P. (2016). A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing. International Journal of Molecular Medicine, 37, 423-428. https://doi.org/10.3892/ijmm.2016.2451
MLA
Idrovo, J. P., Jacob, A., Yang, W. L., Wang, Z., Yen, H. T., Nicastro, J., Coppa, G. F., Wang, P."A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing". International Journal of Molecular Medicine 37.2 (2016): 423-428.
Chicago
Idrovo, J. P., Jacob, A., Yang, W. L., Wang, Z., Yen, H. T., Nicastro, J., Coppa, G. F., Wang, P."A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing". International Journal of Molecular Medicine 37, no. 2 (2016): 423-428. https://doi.org/10.3892/ijmm.2016.2451