Sauromatum guttatum extract promotes wound healing and tissue regeneration in a burn mouse model via up-regulation of growth factors

The American cockroach (Periplaneta americana) is a medicinal insect. Its extract is used clinically to promote wound healing and tissue regeneration, but the effective medicinal components and mechanisms are not yet clear. It has been reported that human thymosin beta 4 (Tβ4) may accelerate skin wound healing, however, the role of P. americana thymosin (Pa-THYs) is still poorly understood. In the present study, we identify and analyze the DNA sequences of Pa-THYs by bioinformatics analysis. Then we clone, express, and purify the Pa-THYs proteins and evaluate the activity of recombinant Pa-THYs proteins by cell migration and proliferation assays in NIH/3T3 cells. To elucidate the role of Pa-THYs in wound healing, a mouse model is established, and we evaluate wound contraction, histopathological parameters, and the expressions of several key growth factors after Pa-THYs treatment. Our results showed that three THY variants were formed by skipping splicing of exons. Pa-THYs could promote fibroblast migration, but have no effect on fibroblast proliferation. In wound repair, Pa-THYs proteins could effectively promote wound healing through stimulating dermal tissue regeneration, angiogenesis, and collagen deposition. On the molecular mechanism, Pa-THYs also stimulated the expression of several key growth factors to promote wound healing. The data suggest that Pa-THYs could be a potential drug for promoting wound repair.

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Macrophage-derived Growth Factors in Wound Healing: Regulation of Growth Factor Production by the Oxygen Microenvironment

American Review of Respiratory Disease ◽

10.1164/ajrccm/140.4.1108 ◽

1989 ◽

Vol 140 (4) ◽

pp. 1108-1111 ◽

Cited By ~ 21

Author(s):

David R. Knighton ◽

Vance D. Fiegel

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Growth Factor ◽

Factor Production ◽

Growth Factor Production ◽

Regulation Of Growth

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VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes

npj Regenerative Medicine ◽

10.1038/s41536-021-00189-1 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Michael J. V. White ◽

Priscilla S. Briquez ◽

David A. V. White ◽

Jeffrey A. Hubbell

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factors ◽

Growth Factor ◽

Mouse Model ◽

Triple Therapy ◽

Nod Mouse ◽

Heparin Binding ◽

Healing Wounds

AbstractChronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123–144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors (eGFs) improved both re-epithelialization and granulation tissue formation. eGFs were even more potent in combination, and the “triple therapy” of vascular endothelial growth factor-A (VEGF-PlGF-2123–144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123–144), and heparin-binding epidermal growth factor (HB-EGF-PlGF-2123–144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound-healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123–144, PDGF-BB-PlGF-2123–144, and HB-EGF-PlGF-2123–144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.

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VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes

10.1101/2021.06.21.449313 ◽

2021 ◽

Author(s):

MICHAEL John Victor WHITE ◽

Priscilla Briquez ◽

David Andrew Victor White ◽

Jeffrey Hubbell

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factors ◽

Growth Factor ◽

Mouse Model ◽

Triple Therapy ◽

Nod Mouse ◽

Heparin Binding ◽

Healing Wounds

Chronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123-144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors improved both re-epithelialization and granulation tissue formation. Engineered growth factors were even more potent in combination, and the *triple therapy* of vascular endothelial growth factor-A (VEGF-PlGF-2123-144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123-144), and heparin-binding epidermal-growth factor (EGF-PlGF-2123-144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123-144, PDGF-BB-PlGF-2123-144, and EGF-PlGF-2123-144 may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.

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Regulation of growth factors-associated cell migration by C-phycocyanin scaffold in dermal wound healing

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.2011.05627.x ◽

2011 ◽

Vol 39 (1) ◽

pp. 13-19 ◽

Cited By ~ 18

Author(s):

Harishkumar Madhyastha ◽

Radha Madhyastha ◽

Yuichi Nakajima ◽

Sayuri Omura ◽

Masugi Maruyama

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Growth Factors ◽

Factors Associated ◽

Dermal Wound Healing ◽

Regulation Of Growth ◽

Dermal Wound

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Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides

International Journal of Molecular Sciences ◽

10.3390/ijms20174072 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4072 ◽

Cited By ~ 2

Author(s):

Leora Goldbloom-Helzner ◽

Dake Hao ◽

Aijun Wang

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factors ◽

Regenerative Medicine ◽

Tissue Regeneration ◽

The Body ◽

Collagen Binding ◽

Developmental Defects ◽

Binding Peptides ◽

Bioactive Surfaces

Collagen is the most widespread extracellular matrix (ECM) protein in the body and is important in maintaining the functionality of organs and tissues. Studies have explored interventions using collagen-targeting tissue engineered techniques, using collagen hybridizing or collagen binding peptides, to target or treat dysregulated or injured collagen in developmental defects, injuries, and diseases. Researchers have used collagen-targeting peptides to deliver growth factors, drugs, and genetic materials, to develop bioactive surfaces, and to detect the distribution and status of collagen. All of these approaches have been used for various regenerative medicine applications, including neovascularization, wound healing, and tissue regeneration. In this review, we describe in depth the collagen-targeting approaches for regenerative therapeutics and compare the benefits of using the different molecules for various present and future applications.

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