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Title
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Fine-sampled Photographic Quantitation of Dermal Wound Healing Senescence in Aged BALB/cByJ Mice and Therapeutic Intervention with FGF-1: Novel photographic quantitation of dermal healing.
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Creator
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Mellers, Alana, Tenorio, Connie, Lacatusu, Diana, Powell, Brett, Patel, Bhavi, Harper, Kathleen, Blaber, Michael
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Abstract/Description
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Objective: Determine quantitative parameters of dermal wound healing senescence in aged BALB/cByJ mice (an important animal model of aging) and evaluate the potential for therapeutic intervention by fibroblast growth factor-1 (FGF-1). Approach: Utilize a novel, non-invasive, fine-sampled photographic methodology to quantify wound healing parameters for healing phases from wounding through to wound closure. Results: Parameters associated with key healing phases were quantified and compared for...
Show moreObjective: Determine quantitative parameters of dermal wound healing senescence in aged BALB/cByJ mice (an important animal model of aging) and evaluate the potential for therapeutic intervention by fibroblast growth factor-1 (FGF-1). Approach: Utilize a novel, non-invasive, fine-sampled photographic methodology to quantify wound healing parameters for healing phases from wounding through to wound closure. Results: Parameters associated with key healing phases were quantified and compared for non-aged and aged cohorts of both sexes. The results identify a sexual dimorphism in dermal wound healing, with non-aged females exhibiting a greater overall healing efficiency compared to males. This enhanced healing in females, however, senesces with age such that healing parameters for aged males and females are statistically indistinguishable. Topical application of FGF-1 was identified as an effective therapeutic intervention to treat dermal healing senescence in aged females. Innovation: The FGF intervention is being analyzed using a new, recently published model. This approach significantly increases the amount of pre-clinical animal data obtainable in wound healing studies, minimizes cohort number compared to (lethal) histological studies, and permits a direct statistical comparison between different healing studies. Conclusion: Quantitative parameters of dermal wound healing, obtained from non-invasive fine-sampled photographic data, identify topical FGF-1 as an effective therapeutic to treat the senescence of dermal healing present in aged female BALB/cByJ mice.
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Date Issued
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2018-06-25
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Identifier
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FSU_libsubv1_scholarship_submission_1529889363_21ee7933
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Format
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Citation
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Title
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Investigating the Dynamics and Polyanion Binding Sites of Fibroblast Growth Factor-1 Using Hydrogen-Deuterium Exchange Mass Spectrometry.
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Creator
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Angalakurthi, Siva K, Tenorio, Connie A, Blaber, Michael, Middaugh, Russell
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Abstract/Description
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In this study, we examined the local dynamics of acidic fibroblast growth factor (FGF-1) as well as the binding sites of various polyanions including poly-sulfates (heparin and low MW heparin) and poly-phosphates (phytic acid and ATP) using hydrogen-deuterium exchange mass spectrometry (HX-MS). For local dynamics, results are analyzed at the peptide level as well as in terms of buried amides employing crystallographic B-factors and compared with a residue level heat map generated from HX-MS...
Show moreIn this study, we examined the local dynamics of acidic fibroblast growth factor (FGF-1) as well as the binding sites of various polyanions including poly-sulfates (heparin and low MW heparin) and poly-phosphates (phytic acid and ATP) using hydrogen-deuterium exchange mass spectrometry (HX-MS). For local dynamics, results are analyzed at the peptide level as well as in terms of buried amides employing crystallographic B-factors and compared with a residue level heat map generated from HX-MS results. Results show that strand 4 and 5 and the turn between them to be the most flexible regions as was previously seen by NMR. On the other hand, the C-terminal strands 8, 9 and 10 appear to be more rigid which is also consistent with crystallographic B-factors as well as local dynamics studies conducted by NMR. Crystal structures of FGF-1 in complex with heparin have shown that heparin binds to N-terminal Asn18 and to C-terminal Lys105, Tryp107, Lys112, Lys113, Arg119, Pro121, Arg122, Gln127 and Lys128 indicating electrostatic forces as dominant interactions. Heparin binding as determined by HX-MS is consistent with crystallography data. Previous studies have also shown that other polyanions including low MW heparin, phytic acid and ATP dramatically increase the thermal stability of FGF-1. Using HX-MS, we find other poly anions tested bind in a similar manner to heparin, primarily targeting the turns in the lysine rich C-terminal region of FGF-1 along with two distinct N-terminal regions that contains lysines and arginines/ histidines. This confirms the interactions between FGF-1 and polyanions are primary directed by electrostatics.
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Date Issued
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2018-04-05
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Identifier
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FSU_libsubv1_scholarship_submission_1523040928_8f170751
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Format
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Citation
