Off-campus WSU users: To download campus access dissertations, please use the following link to log into our proxy server with your WSU access ID and password, then click the "Off-campus Download" button below.
Non-WSU users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Pharmaceutical Sciences
First Advisor
Dr. Zhengping Yi
Second Advisor
Dr. Jiemei Wang
Abstract
Diabetes mellitus is a chronic metabolic disorder affecting over 38 million individuals in the United States and hundreds of millions globally. Among its complications, impaired wound healing remains a major clinical challenge, driven by persistent inflammation, oxidative stress, and a delayed transition to the proliferative phase of repair. These disruptions result in chronic, non-healing wounds with elevated risk of infection and tissue degeneration, placing a significant burden on healthcare systems. Despite progress in wound care technologies, current therapies often fail to correct the underlying molecular dysfunctions, underscoring the need for targeted interventions that restore normal healing trajectories.This study explores the proteomic and phosphoproteomic landscapes of wound tissues from diabetic db/db mice and human endothelial cells treated with a small-molecule coformulation of trans-resveratrol (tRES) and hesperetin (HESP)—compounds previously shown to accelerate tissue repair. By profiling protein and phosphoprotein expression changes in response to treatment, we aim to uncover mechanistic insights and identify candidate pathways for therapeutic intervention. Proteomic analysis revealed substantial differences in protein expression between diabetic and healthy conditions, with tRES+HESP treatment restoring the abundance of seven proteins in mouse wound tissue and six proteins in human endothelial cells. Phosphoproteomic profiling identified five phosphoproteins in mouse tissue and six in human cells whose phosphorylation states were similarly normalized. Pathway enrichment analysis indicated that these proteins are involved in key biological processes including cytoskeletal organization, immune regulation, RNA metabolism, mitochondrial function, lipid processing, and extracellular matrix remodeling. Furthermore, the treatment modulated critical signaling pathways such as PI3K/AKT, NFκB-mediated inflammation, and TGF-β signaling, all of which are essential for resolving inflammation and promoting tissue regeneration. Collectively, these findings demonstrate that tRES+HESP exerts broad molecular effects on wound healing pathways, offering a promising therapeutic strategy for restoring regenerative capacity in diabetic wounds. Future studies will be required to validate these molecular targets and assess their translational potential in clinical settings.
Recommended Citation
Jaiswal, Ruchi, "Modulation Of Global Proteome And Phosphoproteome By Trans-Resveratrol And Hesperetin Coformulation In Diabetic Wound" (2025). Wayne State University Dissertations. 4160.
https://digitalcommons.wayne.edu/oa_dissertations/4160