A bioinformatic analysis of microarray data on the effects of diabetes on increasing mRNA levels of pro-apoptotic genes that contribute to impaired healing
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Abstract
The purpose of the current research was to determine if diabetes had a significant
effect on the healing process of an injury caused by bacteria, and to identify the potential
mechanisms involved. To achieve the objective of the study, diabetic mice and
normoglycemic mice (n=6) were inoculated with Porphyromonas gingivalis (P. gingivalis).
Scalp tissue was excised eight days later, and either fixed for histological sections or snap
frozen for molecular analysis. Histological analysis from the inoculated site revealed that
diabetes increased apoptosis of fibroblast and bone lining cells when compared to
normoglycemic animals (p<0.05; n=6). When the pancaspase inhibitor z-V AD-fink (Nbenzyloxycarbonyl-
Val-Ala-Asp-fluoromethylketone) was used to inhibit diabetes-enhanced
apoptosis, several parameters of healing, including fibroblast density and ir.tcreased matrix
formation were observed. Total RNA from the excised scalp tissue obtained from
normoglycemic (n=6) and diabetic (n=6) was subjected to RNA profiling, using a Mouse
Genome 430 2.0 Array to determine how diabetes affects the global expression of various
genes involved in wound healing. The microarray analysis revealed that out of 221
differentially expressed apoptotic genes; diabetes caused more than a twofold induction of 71
genes that directly or indirectly regulate apoptosis. Most of the healing, angiogenesis, growth
factor, matrix and immune response genes are highly expressed at 5 days but there is only a
moderate increase at 8 days signifying that early defense and wound healing process initiated
at 5 days and almost completed at 8 days. Therefore, it was inferred that day 5 is important
to study wound healing. And also diabetes-enhanced apoptosis is an important mechanism ... [TRUNCATED]
Description
Thesis (MSD)--Boston University, Goldman School of Dental Medicine, 2007 (Dept. of Endodontics).
Includes bibliography: leaves 63-73.
Includes bibliography: leaves 63-73.
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