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Characterisation of Cutaneous Wound Healing Process in Naked Mole Rats
Fatima, Iqra
Fatima, Iqra
Publication Date
2022
End of Embargo
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
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Accepted for publication
Institution
University of Bradford
Department
School of Chemistry and Biosciences. Faculty of Life Sciences
Awarded
2022
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Abstract
Being the longest-lived rodent, naked mole-rats (NMR; Heterocephalus glaber) are
an exceptional model for biogerontological research. However, unlike other
rodents, not much is known about their wound healing process. To investigate that,
full-thickness wounds were created in the back skin of naked mole rats. Our initial
data confirmed that wound closure in NMR skin was achieved primarily by reepithelialization
and granulation tissue formation, with only ~26% wound
contraction, making them an excellent model to study human cutaneous wound
healing. Similar to mice and human skin, changes in wound epithelial tongue
included progressive enlargement of wound epithelium, increased proliferation and
changes in the expression pattern of epidermal markers including K14, K17,
integrin α6 and E-cadherin. Further analysis revealed characteristics of reduced scarring in NMR wounds including low collagen I to III ratio, increased HA
expression (HMW) and increased fibronectin expression. Transcriptional profiling
of TGFβ isoforms and different pro/anti-inflammatory cytokines revealed a balance
in the expression and repression of different cytokines, potentially contributing into
reduced scarring. Comparison of RNA-seq data from NMR and human fullthickness
wounds revealed a delay in the activation of important biological
processes and pathways in NMR skin in response to injury. Further analysis based on cultured human and NMR cells revealed differential regulation of TGFβ
signalling pathway between both species. 3-D collagen gel contraction assay
revealed that NMR fibroblast showed noticeable contraction but independently of
TGFβ treatment, while human fibroblast showed marked increased in gel
contraction in the presence of TGFβ. In conclusion, NMR can serve as a very useful
model to study human cutaneous wound healing. The reduced scarring in NMR
could be a result of multiple factors including HMW-HA, balanced cytokine
expression and differential regulation of different TGFβ cytokines as observed in
the in vitro studies.
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Type
Thesis
Qualification name
PhD