Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase

Misiura, Magdalena; Guszczyn, Tomasz; Ościłowska, Ilona; Baszanowska, Weronika; Pałka, Jerzy; Miltyk, Wojciech

doi:10.3390/ijms22020936

Cited by 19 publications

(17 citation statements)

References 44 publications

(42 reference statements)

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“…Under chemically-induced cell disruption PEPD concentration significantly increases ( Yang et al, 2013 ). Another possible source of prolidase can be platelets in the bloodstream ( Guszczyn et al, 2017 ; Misiura et al, 2021a ). Platelets are essential players in the initial stage of inflammation as they carry various inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing

Nizioł

Ościłowska

Baszanowska

et al. 2022

Front. Mol. Biosci.

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This study was conducted to investigate the proliferative capacity of recombinant human prolidase (rhPEPD) in a human model of inflammation induced by IL-1β in HaCaT keratinocytes. In this report, we provide evidence that IL-1β stimulates keratinocyte proliferation, and rhPEPD significantly augmented this process through activation of epidermal growth factor receptor (EGFR) and downstream signaling proteins as phosphorylated Akt, ERK1/2, and STAT3, which are implicated in keratinocyte migration, proliferation, and epithelialization during the wound healing process. Inhibition of PEPD-dependent EGFR signaling by gefitinib supported the finding. Moreover, during activation of EGFR in the presence of IL-1β the epithelial-to-mesenchymal transition (EMT) occurred via downregulation of E-cadherin and upregulation of N-cadherin. The phenomenon was accompanied by an increase in the activity of matrix metalloproteinase-9 (MMP-9), suggesting extracellular matrix (ECM) remodeling during the inflammatory process. MMP-9 activation may result from nuclear translocation of NF-κB through IKK-mediated IκBα degradation. Interestingly, some mutated variants of PEPD (rhPEPD-G448R, rhPEPD-231delY, and rhPEPD-E412K) evoked the ability to induce EGFR-dependent HaCaT cell proliferation. To the best of our knowledge, this is the first report on the cross-talk between PEPD and IL-1β in the process of keratinocyte proliferation. The data suggest that both enzymatically active and inactive rhPEPD may activate EGFR-dependent cell growth in an experimental model of inflammation in HaCaT keratinocytes and the knowledge may be useful for further approaches for therapy of wound healing disorders.

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Section: Discussionmentioning

confidence: 99%

Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing

Nizioł

Ościłowska

Baszanowska

et al. 2022

Front. Mol. Biosci.

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“…Cells were cultured in FBS-free DMEM with Cx (5–25 µM) for 24 h. The procedure for harvesting the cells was performed as previously described [ 31 ]. The supernatant was aliquoted and stored at −80 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was carried out as described by Misiura et al [ 31 ]. The membranes were incubated with primary antibodies diluted 1000 times in 5% bovine serum albumin (Sigma Aldrich, Saint Louis, MO, USA) in TBS-T (20 mM Tris, 150 mM NaCl, 0.1% Tween-20, pH 7.6).…”

Section: Methodsmentioning

confidence: 99%

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PRODH/POX-Dependent Celecoxib-Induced Apoptosis in MCF-7 Breast Cancer

et al. 2021

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Celecoxib (Cx), an inhibitor of cyclooxygenase 2, induces apoptosis of cancer cells. However, the mechanism of the chemopreventive effect remains not fully understood. We aimed to investigate the role of PRODH/POX that is involved in the regulation of apoptosis induced by celecoxib. MCF-7 breast cancer cell line and the corresponding MCF-7 cell line with silenced PRODH/POX (MCF-7shPRODH/POX) were used. The effects of Cx on cell viability, proliferation, and cell cycle were evaluated. The expressions of protein markers for apoptosis (Bax, caspase 9, and PARP) and autophagy (Atg5, Beclin 1, and LC3A/B) were investigated by Western immunoblotting. To analyze the proline metabolism, collagen biosynthesis, prolidase activity, proline concentration, and the expression of proline-related proteins were evaluated. The generation of ATP, ROS, and the ratio of NAD+/NADH and NADP+/NADPH were determined to test the effect of Cx on energetic metabolism in breast cancer cells. It has been found that Cx attenuated MCF-7 cell proliferation via arresting the cell cycle. Cx induced apoptosis in MCF-7 breast cancer cells, while in MCF-7shPRODH/POX, autophagy occurred more predominantly. In MCF-7 breast cancer cells, Cx affected proline metabolism through upregulation of proline biosynthesis, PRODH/POX and PYCRs expressions, PEPD activity, and downregulation of collagen biosynthesis. In MCF-7shPRODH/POX clones, these processes, as well as energetic metabolism, were remarkably suppressed. The data for the first time suggest that celecoxib induces apoptosis through upregulation of PRODH/POX in MCF-7 breast cancer cells.

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“…The cell cycle of C32 WT and C32 POX− cells upon metformin treatment (0-20 mM) for 24 h was analyzed as previously described [69].…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line

Ościłowska

Rolkowski

Baszanowska

et al. 2022

IJMS

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The role of proline dehydrogenase/proline oxidase (PRODH/POX) in the mechanism of antineoplastic activity of metformin (MET) was studied in C32 melanoma cells. PRODH/POX is a mitochondrial enzyme-degrading proline that is implicated in the regulation of cancer cell survival/apoptosis. The enzyme is activated by AMP kinase (AMPK). It has been found that MET induced a significant decrease in cell viability and DNA biosynthesis accompanied by an increase in the expressions of AMPK and PRODH/POX in C32 cells. The mechanism for MET-dependent cytotoxicity on C32 cells was found at the level of PRODH/POX-induced ROS generation and activation of Caspase-3 and Caspase-9 expressions in these cells. The effects were not observed in MET-treated PRODH/POX knock-out C32 cells. Of interest is an MET-dependent increase in the concentration of proline, which is a substrate for PRODH/POX. This phenomenon is due to the MET-dependent inhibition of collagen biosynthesis, which is the main proline-utilizing process. It has been found that the underlying mechanism of anticancer activity of MET involves the activation of AMPK, PRODH/POX, increase in the cytoplasmic concentration of proline, inhibition of collagen biosynthesis, and stimulation of PRODH/POX-dependent ROS generation, which initiate the apoptosis of melanoma cells.

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Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase

Cited by 19 publications

References 44 publications

Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing

Recombinant Prolidase Activates EGFR-Dependent Cell Growth in an Experimental Model of Inflammation in HaCaT Keratinocytes. Implication for Wound Healing

PRODH/POX-Dependent Celecoxib-Induced Apoptosis in MCF-7 Breast Cancer

Proline Dehydrogenase/Proline Oxidase (PRODH/POX) Is Involved in the Mechanism of Metformin-Induced Apoptosis in C32 Melanoma Cell Line

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