scholarly journals Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts

2021 ◽  
Vol 22 (2) ◽  
pp. 942
Author(s):  
Weronika Baszanowska ◽  
Magdalena Misiura ◽  
Ilona Oscilowska ◽  
Jerzy Palka ◽  
Wojciech Miltyk
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Experimental Model ◽  
Growth Factor Receptor ◽  
Β1 Integrin ◽  
Collagen Biosynthesis ◽  
Cultured Fibroblasts ◽  
Downstream Signaling ◽  
Epidermal Growth ◽  
And Migration

The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1–100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and β1-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimulated proliferation and migration of fibroblasts via activation of the EGFR-downstream PI3K/Akt/mTOR signaling pathway. Simultaneously, PEPD stimulated the expression of β1-integrin and IGF-1 receptors and proteins downstream to these receptors such as FAK, Grb2, and ERK1/2. Collagen biosynthesis was increased in control and “wounded” fibroblasts under PEPD treatment. The data suggest that PEPD-induced EGFR signaling may serve as a new attempt to therapy wound healing.

scholarly journals Prolidase Stimulates Proliferation and Migration through Activation of the PI3K/Akt/mTOR Signaling Pathway in Human Keratinocytes

2020 ◽  
Vol 21 (23) ◽  
pp. 9243
Author(s):  
Magdalena Misiura ◽  
Weronika Baszanowska ◽  
Ilona Ościłowska ◽  
Jerzy Pałka ◽  
Wojciech Miltyk
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Keratinocytes ◽  
Immunocytochemical Staining ◽  
Β1 Integrin ◽  
Collagen Biosynthesis ◽  
Downstream Signaling ◽  
And Migration ◽  
Proliferation And Migration

Recent reports have indicated prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR). Since this receptor is involved in the promotion of cell proliferation, growth, and migration, we aimed to investigate whether prolidase may participate in wound healing in vitro. All experiments were performed in prolidase-treated human keratinocytes assessing cell vitality, proliferation, and migration. The expression of downstream signaling proteins induced by EGFR, insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1), and β1-integrin receptors were evaluated by Western immunoblotting and immunocytochemical staining. To determine collagen biosynthesis and prolidase activity radiometric and colorimetric methods were used, respectively. Proline content was determined by applying the liquid chromatography coupled with mass spectrometry. We found that prolidase promoted the proliferation and migration of keratinocytes through stimulation of EGFR-downstream signaling pathways in which the PI3K/Akt/mTOR axis was involved. Moreover, PEPD upregulated the expression of β1-integrin and IGF-1 receptors and their downstream proteins. Proline concentration and collagen biosynthesis were increased in HaCaT cells under prolidase treatment. Since extracellular prolidase as a ligand of EGFR induced cell growth, migration, and collagen biosynthesis in keratinocytes, it may represent a potential therapeutic approach for the treatment of skin wounds.

scholarly journals The Motile Breast Cancer Phenotype Roles of Proteoglycans/Glycosaminoglycans

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Dragana Nikitovic ◽  
Katerina Kouvidi ◽  
Kallirroi Voudouri ◽  
Aikaterini Berdiaki ◽  
Evgenia Karousou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Downstream Signaling ◽  
Insulin Growth Factor ◽  
Cancer Pathogenesis ◽  
Cellular Mediators ◽  
Epidermal Growth ◽  
Cancer Phenotype ◽  
Insulin Growth Factor Receptor

The consecutive stages of cancer growth and dissemination are obligatorily perpetrated through specific interactions of the tumor cells with their microenvironment. Importantly, cell-associated and tumor microenvironment glycosaminoglycans (GAGs)/proteoglycan (PG) content and distribution are markedly altered during tumor pathogenesis and progression. GAGs and PGs perform multiple functions in specific stages of the metastatic cascade due to their defined structure and ability to interact with both ligands and receptors regulating cancer pathogenesis. Thus, GAGs/PGs may modulate downstream signaling of key cellular mediators including insulin growth factor receptor (IGFR), epidermal growth factor receptor (EGFR), estrogen receptors (ERs), or Wnt members. In the present review we will focus on breast cancer motility in correlation with their GAG/PG content and critically discuss mechanisms involved. Furthermore, new approaches involving GAGs/PGs as potential prognostic/diagnostic markers or as therapeutic agents for cancer-related pathologies are being proposed.

scholarly journals Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins

2016 ◽  
Vol 291 (11) ◽  
pp. 5528-5540 ◽  
Author(s):  
Tom Ronan ◽  
Jennifer L. Macdonald-Obermann ◽  
Lorel Huelsmann ◽  
Nicholas J. Bessman ◽  
Kristen M. Naegle ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Signaling Proteins ◽  
Downstream Signaling ◽  
Epidermal Growth

scholarly journals Loliolide Presents Antiapoptosis and Antiscratching Effects in Human Keratinocytes

2019 ◽  
Vol 20 (3) ◽  
pp. 651 ◽  
Author(s):  
Sang Park ◽  
Dong Kim ◽  
Sunggyu Kim ◽  
Laura Lorz ◽  
Eunju Choi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Keratinocyte Growth Factor ◽  
Growth Factor Receptor ◽  
Ethanol Extract ◽  
Human Keratinocytes ◽  
Freshwater Algae ◽  
And Migration ◽  
Induced Apoptosis

Loliolide is a monoterpenoid hydroxylactone present in freshwater algae that has anti-inflammatory and antiaging activity; however, its effects on ultraviolet-damaged skin have yet to be elucidated. This study investigated the antiapoptosis and wound-healing effects of loliolide using HaCaT cells (a human keratinocyte cell line). Loliolide inhibited the expression of reactive oxygen species (ROS) induced by ultraviolet radiation as well as wrinkle formation-related matrix metalloproteinase genes and increased the expression of the damage repair-related gene SIRT1. The apoptosis signaling pathway was confirmed by Western blot analysis, which showed that loliolide was able to reduce the expression of caspases 3, 8, and 9, which are related to ROS-induced apoptosis. In addition, Western blotting, reverse-transcription polymerase chain reaction (PCR), and real-time PCR analyses showed that loliolide enhanced the expression of the epidermal growth factor receptor signaling pathway (PI3K, AKT) and migration factors, such as K6, K16, and K17; keratinocyte growth factor; and inflammatory cytokines, such as interleukin (IL)-1, IL-17, and IL-22 expressed during the cellular scratching process, suggesting a putative wound-healing ability. Because of the antiapoptosis and antiscratching effects on skin of both loliolide and loliolide-rich Prasiola japonica ethanol extract, we consider the former to be an important compound used in the cosmeceutical industry.

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