Document Type

Thesis - Open Access

Award Date

2018

Degree Name

Master of Science (MS)

Department / School

Biology and Microbiology

First Advisor

Mark Messerli

Abstract

Chronic wounds are wounds that do not heal within 30 days and often they can last over a year. Interference in any of the wound healing stages may hinder the process. Some of the local and systemic factors such as infection, old age, diabetes, AIDS, and the regular application of corticoids may also have negative effects on the healing process. Cell proliferation is an important phase in epidermal wound healing in which surviving epithelial cells replicate independently into daughter cells through mitosis and maintain a balance between cell growth and cell loss during the cell cycle. Physical and chemical stimuli play important roles in regulating cell proliferation through activating intracellular signal transduction pathways. A physical stimulus which enhances skin cell proliferation relies on mechanical stretch. However, the mechanism(s) by which cells sense and respond to mechanical stimulation remain(s) unknown. Most research regarding sensing of mechanical stimuli emphasizes the role of cellular membrane proteins including channels, integrins, and receptors for growth factors. Channels could be selective or non-selective, or mechanosensitive for inorganic ions or small molecules, with high permeability to ions such as sodium, potassium, calcium, and magnesium. Mechanosensitive channels (MSCs) are present in many cell types including epidermal keratinocytes. MSCs play a crucial role as a mechanosensors which convert mechanical stimuli into electrical or chemical signals. MSCs may affect cells through the movement of specific ions, such as calcium, across the plasma membrane. Cytosolic calcium in the form of steady or transient changes is required for cell cycle progression, cell proliferation and cell division. In other words, Ca2+ influx is required for mechanosensitive cell proliferation in human keratinocytes. In this study, we monitored the proliferation rate of stretched cells and observed that mechanical stretching induces a higher percentage of keratinocytes into S-phase. Proliferation was reduced or inhibited in the absence of extracellular Ca2+ or when Ca2+ influx was blocked, respectively. Many pharmacological inhibitors of MSCs were screened to evaluate their effect on cell proliferation and the results demonstrate that blockage of the mechanosensitive ATP channel, pannexin, significantly inhibited proliferation. Identification of a pathway that promotes proliferation of keratinocytes provides us with a target for a chemical treatment that speeds proliferation and promotes wound healing.

Library of Congress Subject Headings

Wound healing.
Keratinocytes.
Cell proliferation.
Cellular signal transduction.

Description

Includes bibliographical references

Format

application/pdf

Number of Pages

60

Publisher

South Dakota State University

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Rights Statement

In Copyright