Fibroblast Growth Factor-Peptide Improves Barrier Function and Proliferation in Human Keratinocytes After Radiation

Journal Article · Thu Sep 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2011.02.004· OSTI ID:21587700

Kunzhong, Zhang ^[1]; Yeping, Tian ^[2]; Liangjie, Yin; Mei, Zhang ^[3]; Beck, Lisa A ^[4]; Zhang, Bingrong; Okunieff, Paul ^[3]; Vidyasagar, Sadasivan ^[3]

---

1. Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York 14642 (United States)
2. Second Military Medical College, Shanghai, P.R. China 200433 (China)
3. Department of Radiation Oncology, University of Florida, Gainesville Florida 32610 (United States)
4. Department of Dermatology, University of Rochester Medical Center, Rochester, New York 14642 (United States)

Purpose: Epidermal keratinocytes, which can be severely damaged after ionizing radiation (IR), are rapid turnover cells that function as a barrier, protecting the host from pathogenic invasion and fluid loss. We tested fibroblast growth factor-peptide (FGF-P), a small peptide derived from the receptor-binding domain of FGF-2, as a potential mitigator of radiation effects via proliferation and the barrier function of keratinocytes. Methods and Materials: Keratinocytes isolated from neonatal foreskin were grown on transwells. After being exposed to 0, 5, or 10 Gy IR, the cells were treated with a vehicle or FGF-P. The permeability of IR cells was assessed by using transepithelial electrical resistance (TEER) and a paracellular tracer flux of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) with Ussing chambers. The cell proliferation was measured with yellow tetrazolium salt (MTT) and tritiated thymidine ([{sup 3}H]-TdR) assays. The phosphorylation of extracellular signal-regulated kinases (ERK) was measured in an enzyme-linked immunosorbent (ELISA)-like assay, and the proteins related to tight junctions (TJ) and adherens junctions (AJ) were examined with Western blotting. We used a mouse model to assess the ability of FGF-P to promote the healing of skin {beta} burns created with a strontium applicator. Results: We found (1) FGF-P reduced the permeability of irradiated keratinocytes, as evidenced by increased TEER and decreased diffusion of FITC-BSA, both associated with the regulation of different proteins and levels of TJ and AJ; and (2) FGF-P enhanced the proliferation of irradiated keratinocytes, as evidenced by increased MTT activity and [{sup 3}H]-TdR incorporation, which was associated with activation of the ERK pathway; and (3) FGF-P promoted the healing of skin {beta} burns. Conclusions: FGF-P enhances the barrier function, including up-regulation of TJ proteins, increases proliferation of human keratinocytes, and accelerates the healing of skin {beta} burns. FGF-P is a promising mitigator that improves the proliferation and barrier function of keratinocytes after IR.

• OSTI ID: 21587700
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 81, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2011.02.004; PII: S0360-3016(11)00234-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALBUMINS
CELL PROLIFERATION
ENZYME IMMUNOASSAY
FIBROBLASTS
GROWTH FACTORS
HEALING
IONIZING RADIATIONS
PEPTIDES
RADIATION BURNS
RADIOTHERAPY
SKIN
TRITIUM
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOASSAY
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BODY
BURNS
CONNECTIVE TISSUE CELLS
DISEASES
HYDROGEN ISOTOPES
IMMUNOASSAY
INJURIES
ISOTOPES
LIGHT NUCLEI
LOCAL RADIATION EFFECTS
MEDICINE
MITOGENS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIATION EFFECTS
RADIATION INJURIES
RADIATIONS
RADIOISOTOPES
RADIOLOGY
SOMATIC CELLS
THERAPY
YEARS LIVING RADIOISOTOPES