Abstract

Decubitus and diabetic foot ulcers remain as important clinical challenges with significant socioeconomic impact. Both are individual forms of chronic wounds with diverse proximal ethiopathogenic triggers. This study aimed to characterize and compare the main histological features as the transcriptional expression profile of a set of wound-healing relevant genes of the ulcers’ granulation tissue. Following patients’ consent, biopsies were collected from sacrolumbar pressure ulcers (N=5, stage IV) and diabetic foot ulcers (N=9, both of neuropathic and ischemic origin) with clean, non-infected granulation tissue. Biopsies fragments were processed for histological analysis and for RNA extraction and subsequent transcriptional expression characterization via RT-PCR. The group of targeted genes included cell proliferation control, extracellular matrix, glucose metabolism, anabolismsurvival, as anti-hypoxia and anti-oxidant defense. Gene expression was determined, normalized with an internal housekeeping gene, and statistically compared. Each class of chronic ulcer granulation tissue: decubitus, and diabetics’ ischemic and neuropathic proved to develop a particular histological pattern thus establishing individual differences. Moreover, diabetes appeared to significantly reduce the expression of numerous genes irrespective to their biological significance. Most importantly, we found that diabetic granulation tissue cells exhibit a sort of “genetic or epigenetic imprinting” for the expression of glucose-metabolism related genes which are deeply involved in type-2 diabetes pathophysiology. Our data indicate that in addition to a protracted inflammation and abnormal angiogenesis, diabetic granulation tissue cells are affected by gene expression failures that may lead to a negative pro-anabolic and energetic balance.

Highlights

  • Pressure or decubitus ulcers (PU) and diabetic foot ulcers (DFU) are among the most common chronic wounds representing individual clinical entities but sharing a significant socioeconomic impact [1]

  • The study population is small, the racial profile is representative of the Cuban ethnicity and for the case of diabetics; the basic disease duration almost tripled the one detected for pressure ulcers

  • The major limitation of this work resides in the reduced number of samples of chronic ulcers studied

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Summary

Introduction

Pressure or decubitus ulcers (PU) and diabetic foot ulcers (DFU) are among the most common chronic wounds representing individual clinical entities but sharing a significant socioeconomic impact [1]. These chronic ulcers translate in systemic repercussion as they may act as pro-inflammatory and pro-oxidant organs super-imposed to a host that could evolve to a chronic low-grade inflammatory response [2]. Its medical history dates back to the renaissance when the French surgeon Ambrose Paré enlisted; nutrition, pain relief and debridement as key factors to heal these ulcers It is not quite different than the present modality to some extent [3]. A large percent of grades 3 and 4 pressure ulcers evolve to chronification and lead the patient to death due to ulcer complications such as sepsis or osteomyelitis [4]

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