A bioinformatic analysis of microarray data on the effects of diabetes on increasing mRNA levels of pro-apoptotic genes that contribute to impaired healing
Kandru, Suneel C.
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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]
Thesis (MSD)--Boston University, Goldman School of Dental Medicine, 2007 (Dept. of Endodontics).Includes bibliography: leaves 63-73.
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