Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing

Chronic diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus, often leading to amputation, increased morbidity, and a substantial financial burden. Even with the advancements in the treatment of DFU, the risk of amputation still exists, and this occurs due to the presence...

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Main Authors: Jacob Smith, Vikrant Rai
Format: Article
Language:English
Published: MDPI AG 2024-08-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/9/1939
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author Jacob Smith
Vikrant Rai
author_facet Jacob Smith
Vikrant Rai
author_sort Jacob Smith
collection DOAJ
description Chronic diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus, often leading to amputation, increased morbidity, and a substantial financial burden. Even with the advancements in the treatment of DFU, the risk of amputation still exists, and this occurs due to the presence of gangrene and osteomyelitis. Nonhealing in a chronic DFU is due to decreased angiogenesis, granulation tissue formation, and extracellular matrix remodeling in the presence of persistent inflammation. During wound healing, the proliferation and migration of fibroblasts, smooth muscle cells, and keratinocytes play a critical role in extracellular matrix (ECM) remodeling, angiogenesis, and epithelialization. The molecular factors regulating the migration, proliferation, and differentiation of these cells are scarcely discussed in the literature. The literature review identifies the key factors influencing the proliferation, migration, and differentiation of fibroblasts, keratinocytes, and vascular smooth muscle cells (VSMCs), which are critical in wound healing. This is followed by a discussion on the various novel factors regulating the migration, proliferation, and differentiation of these cells but not in the context of wound healing; however, they may play a role. Using a network analysis, we examined the interactions between various factors, and the findings suggest that the novel factors identified may play a significant role in promoting angiogenesis, granulation tissue formation, and extracellular matrix remodeling during wound healing or DFU healing. However, these interactions warrant further investigation to establish their role alone or synergistically.
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spelling doaj-art-dc56df3deba94645a1b0a2ecb19c6a932025-08-20T01:56:10ZengMDPI AGBiomedicines2227-90592024-08-01129193910.3390/biomedicines12091939Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound HealingJacob Smith0Vikrant Rai1Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USAChronic diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus, often leading to amputation, increased morbidity, and a substantial financial burden. Even with the advancements in the treatment of DFU, the risk of amputation still exists, and this occurs due to the presence of gangrene and osteomyelitis. Nonhealing in a chronic DFU is due to decreased angiogenesis, granulation tissue formation, and extracellular matrix remodeling in the presence of persistent inflammation. During wound healing, the proliferation and migration of fibroblasts, smooth muscle cells, and keratinocytes play a critical role in extracellular matrix (ECM) remodeling, angiogenesis, and epithelialization. The molecular factors regulating the migration, proliferation, and differentiation of these cells are scarcely discussed in the literature. The literature review identifies the key factors influencing the proliferation, migration, and differentiation of fibroblasts, keratinocytes, and vascular smooth muscle cells (VSMCs), which are critical in wound healing. This is followed by a discussion on the various novel factors regulating the migration, proliferation, and differentiation of these cells but not in the context of wound healing; however, they may play a role. Using a network analysis, we examined the interactions between various factors, and the findings suggest that the novel factors identified may play a significant role in promoting angiogenesis, granulation tissue formation, and extracellular matrix remodeling during wound healing or DFU healing. However, these interactions warrant further investigation to establish their role alone or synergistically.https://www.mdpi.com/2227-9059/12/9/1939diabetic foot ulcerwound healingangiogenesisECM remodelingcell migrationcell proliferation
spellingShingle Jacob Smith
Vikrant Rai
Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
Biomedicines
diabetic foot ulcer
wound healing
angiogenesis
ECM remodeling
cell migration
cell proliferation
title Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
title_full Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
title_fullStr Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
title_full_unstemmed Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
title_short Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing
title_sort novel factors regulating proliferation migration and differentiation of fibroblasts keratinocytes and vascular smooth muscle cells during wound healing
topic diabetic foot ulcer
wound healing
angiogenesis
ECM remodeling
cell migration
cell proliferation
url https://www.mdpi.com/2227-9059/12/9/1939
work_keys_str_mv AT jacobsmith novelfactorsregulatingproliferationmigrationanddifferentiationoffibroblastskeratinocytesandvascularsmoothmusclecellsduringwoundhealing
AT vikrantrai novelfactorsregulatingproliferationmigrationanddifferentiationoffibroblastskeratinocytesandvascularsmoothmusclecellsduringwoundhealing