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A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Pathological insights into cell death pathways in diabetic wound healing
Kannan Harithpriya1, Srinivasan Kaussikaa1, Srikanth Kavyashree1
1Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, TN 603210, United States.
Abstract:
Diabetic foot ulcers (DFUs) are a microvascular complication that affects almost 21 % of the diabetic population. DFUs are characterized by lower limb abnormalities, chronic inflammation, and a heightened hypoxic environment. The challenge of healing these chronic wounds arises from impaired blood flow, neuropathy, and dysregulated cell death processes. The pathogenesis of DFUs involves intricate mechanisms of programmed cell death (PCD) in different cell types, which include keratinocytes, fibroblasts, and endothelial cells. The modes of cell death comprise apoptosis, autophagy, ferroptosis, pyroptosis, and NETosis, each defined by distinct biochemical hallmarks. These diverse mechanisms contribute to tissue injury by inducing neutrophil extracellular traps and generating cellular stressors like endoplasmic reticulum stress, oxidative stress, and inflammation. Through a comprehensive review of experimental studies identified from literature databases, this review synthesizes current knowledge on the critical signaling cascades implicated in programmed cell death within the context of diabetic foot ulcer pathology.
Insights
Diabetic foot ulcers involve complex cell death pathways. Understanding programmed cell death (PCD) mechanisms like apoptosis and ferroptosis is key to healing these chronic wounds.
Area of Science:
- Cell Biology
- Diabetology
- Wound Healing Research
Background:
- Diabetic foot ulcers (DFUs) affect 21% of diabetics, stemming from microvascular issues.
- DFUs present with lower limb abnormalities, chronic inflammation, and hypoxia.
- Impaired blood flow, neuropathy, and dysregulated cell death hinder DFU healing.
Purpose of the Study:
- To review programmed cell death (PCD) mechanisms in DFU pathogenesis.
- To synthesize knowledge on signaling cascades in DFU cell death.
- To understand the role of diverse cell death modes in DFU pathology.
Main Methods:
- Comprehensive literature review of experimental studies.
- Analysis of signaling pathways in programmed cell death.
- Identification of biochemical hallmarks for apoptosis, autophagy, ferroptosis, pyroptosis, and NETosis.
Main Results:
- Programmed cell death (PCD) involves apoptosis, autophagy, ferroptosis, pyroptosis, and NETosis in DFU cells (keratinocytes, fibroblasts, endothelial cells).
- These cell death modes contribute to tissue injury via neutrophil extracellular traps and cellular stressors.
- Endoplasmic reticulum stress, oxidative stress, and inflammation are key contributors.
Conclusions:
- Programmed cell death (PCD) is central to diabetic foot ulcer (DFU) pathogenesis.
- Diverse cell death pathways significantly impact DFU progression and healing challenges.
- Further research into these signaling cascades may reveal novel therapeutic targets for DFUs.
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