Histological and Transcriptional Expression differences between Diabetic Foot and Pressure Ulcers

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. J ou rna l o f D ia be tes & M e ta bolism

Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face

“…In lungs of IPF patients there is a downregulation of key enzymes involved in glycolysis, mitochondrial β-oxidation and tricarboxylic acid cycle [ 61 ], the same phenomenon that is observed in granulation tissue from diabetic foot ulcers [ 62 ]. From a histological point of view, pulmonary capillaries show thickening of the basal lamina [ 63 ], also characteristic of ischemic and neuropathic diabetic foot ulcers, which exhibit arteriolar wall thickening and dense fibrotic matrix infiltrated with inflammatory cells [ 64 ].…”

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

“…The driving forces behind the "inheritance" of these progeroid morphological traits are likely associated to an epigenetic senescence signature (221). 2) Similarly, diabetic granulation tissue although being a "de novo" and short-lived "welding tissue, " its cells exhibit a sort of genetic or epigenetic imprinting for the deranged expression of glucose metabolism-related genes, which are implicated in insulin resistance, cellular senescence, and T2DM pathophysiology (221).…”

Intralesional Infiltrations of Cell-Free Filtrates Derived from Human Diabetic Tissues Delay the Healing Process and Recreate Diabetes Histopathological Changes in Healthy Rats

“…Different evidences converge to indicate that "vascular glycemic memory" (19,20), and other diabetic complications-related histological hallmarks are promoted by underlying abnormal epigenetic programs (21)(22)(23). The fact that various epigenetic mechanisms mediate the intra and transgenerational intra-species inheritance of diabetic-related traits (24,25), render explanation for our earlier observation that diabetic granulation tissue "inherits," and morphologically recreates in a period of days (26) the structural changes of chronic evolution which distinctively characterize diabetic skin histology (27)(28)(29).…”