Expression of cell proliferation cycle negative regulators in fibroblasts of an ischemic diabetic foot ulcer. A clinical case report

Jorge Berlanga-Acosta, Yssel Mendoza-Mari, María Daniela Martínez, Calixto Valdés-Perez, Ariana G. Ojalvo, David G. Armstrong

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Wound chronification and opportunistic infections stand as major factors leading to lower extremities amputations in diabetes. The molecular mechanisms underlying diabetic's torpid healing have not been elucidated. We present the case of a female diabetic patient that after a plantar abscess surgical drainage, tight glycaemia control and infection clearance; the wound bed evolved to chronification with poor matrix accumulation, scant angiogenesis and no evidence of dermo-epidermal contours contraction. Ulcer fibroblasts yet cultured under 'physiological' conditions exhibited a slow and declining proliferative response. Diabetic fibroblasts cycle arrest occurred earlier than non-diabetic counterparts. This in vitro premature arrest-senescence phenotype appeared related to the transcriptional upregulation of p53 and the proto-oncogene c-myc; with a concomitant expression reduction of the survival and cellular growth promoters Akt and mTOR. Importantly, immunocytochemistry of the diabetic ulcer-derived fibroblasts proved nuclear over expression of potent proliferation inhibitors and pro-senescence proteins as p53 phosphorylated on serine-15 and p21Cip(1). In line with this, cyclin D1 appeared substantially underexpressed in these cells. We postulate that the downregulation of the Akt/mTOR/cyclin D1 axis by the proximal activation of p53 and p21 due to stressor factors, impose an arrest/pro-senescence programme that translated in a torpid and slow healing process.

Original languageEnglish (US)
Pages (from-to)232-236
Number of pages5
JournalInternational Wound Journal
Issue number2
StatePublished - Apr 2013


  • Cell cycle
  • Diabetes
  • Fibroblast
  • Foot ulcers
  • Ulcer

ASJC Scopus subject areas

  • Surgery
  • Dermatology


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