Effect of p38 MAPK Inhibition on Apoptosis Marker Expression  in the Process of Peritoneal Adhesion Formation

Shurygina, I. A.; Aushinova, Nataliya; Шурыгин, М. Г.

doi:10.21103/article8(4)_oa15

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…Our main finding is that tissular expression of growth factors during peritoneal wound repair is a biphasic process, with an early phase culminating on day 3 after injury, and a late phase reaching its maximum two weeks after this injury. These results are in line with the expression of proinflammatory cytokines in the abdominal cavity [ 20 ], [ 21 ]. Notably, the second peak at day 14 was usually more pronounced.…”

Section: Discussionsupporting

confidence: 81%

Growth factors in the regulation of reparative response in the presence of peritoneal damage

Shurygina

Шурыгин²,

Rodionova

et al. 2020

Pleura and Peritoneum

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ObjectivesTo study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage.MethodsExperimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively.ResultsTissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14.ConclusionsWe observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.

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Section: Discussionsupporting

confidence: 81%

Growth factors in the regulation of reparative response in the presence of peritoneal damage

Shurygina

Шурыгин²,

Rodionova

et al. 2020

Pleura and Peritoneum

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“…(35) At the same time, a low index for cells with a Ki-67 positive phenotype in the experimental group causes the formation of a Grade 1 adhesion process, estimated at 4 points. This observation of low activity of mitotic processes in fibroblasts in the repair zone when using p38 MAPK blockers (experimental group) is combined in this group with an increase in apoptosis processes, (36) which together determines a low potential for adhesion formation.…”

Section: Discussionmentioning

confidence: 98%

Using Ki-67 Mitotic Activity Markers as a Predictor of the Progression of Adhesions in the Abdominal Cavity

Shurygina¹,

Шурыгин²,

Chepurnykh³

et al. 2020

IJBM

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Background: Ki-67 is a nuclear protein expressed in all proliferating cells of vertebrates during mitotic cycle phases S, G1, G2, and M, except for G0. Studying this marker is widely used to diagnose the proliferative activity of tumors. However, studying Ki-67 in non-neoplastic diseases attracts much less attention among the researchers. The aim of this study was to assess the possibility of using staining for Ki-67 to identify the proliferative potential of fibroblasts during the formation of adhesions in the abdominal cavity (AC). Methods and Results: Experiments were carried out on male Wistar rats. The adhesion process in AC was simulated in the control group (n=25), and in the experimental group (n=25) with the administration of Seroguard®. Animals were sacrificed on Days 1–30, and the severity of the adhesive process in AC was assessed. Histological sections were prepared and stained for Ki-67. It was found that the animals of the control group had increased severity of the adhesive process in AC during the observation. Maximum increase in severity was registered on Day 30 – 12[9-13] points in the control group and 4[4-4] points in the experimental group (P=0.0079). High proliferative activity of fibroblasts in the control group was detected on Days 3, 7, 14 and 30, which may indicate an active division of fibroblasts and the formation of adhesions in the damaged area. In the experimental group, single Ki-67 positive cells were noted during the entire observation period, which may point to a reduced potential for the formation of adhesions. Conclusion: Our study showed the prospects of using Ki-67 staining to determine the severity of the developing adhesive process in AC, and also revealed one of the possible mechanisms that inhibit the formation of the adhesive process when using Seroguard® – a decrease in the mitotic activity of fibroblasts in the area of peritoneal injury.

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“…MAPKs constitute a protein family relaying signal transduction, amplification and integration and thus providing for appropriate physiological responses of mammalian cells, such as proliferation, differentiation, inflammation and apoptosis. (21)(22)(23)(24) One of the MAP kinase subfamilies, p38 MAPK, is known to be activated under stress conditions caused by ultraviolet radiation, heat shock, osmotic stress, lipopolysaccharide, protein synthesis inhibitors, pro-inflammatory cytokines (IL-1, TNF-α, etc. ), and also by certain mitogens realizing the effect through tyrosine kinase receptors in particular.…”

Section: Discussionmentioning

confidence: 99%

Changes in Oxidative Phosphorylation Activity in Fibroblasts at p38 MAPK Pathway Inhibition

Shurygina¹,

Trukhan²,

Дремина³

et al. 2019

IJBM

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Background: Mitochondrial oxidative phosphorylation (OxPhos) accounts for more than 90% of the cellular ATP production, plays the role in reactive oxygen species (ROS) generation and programmed cell death. In addition, it contributes to such cellular processes as proliferation, differentiation and cell aging. Currently, several signaling systems are known to participate in regulation of OxPhos and activity of cytochrome c-oxidase (CcO), the terminal enzyme of the mitochondrial electron transport chain. However, data on mechanisms and key units involved in the signal transduction are still being supplemented. Methods: Peritoneal fibroblasts were isolated from the omentum of Wistar rats by fragmenting the dissected tissue and disaggregating the fragments in collagenase solution (200 U/ml). The primary culture of fibroblasts was cultured in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% Fetal Bovine Serum (FBS), 1% antibiotic/antimycotic at 37°C, 80% RH and 5% СО 2 in Biostation CT, Nikon. To obtain a culture, the fibroblasts were subcultured every 7 days. After the third passage the culture was treated with SB203580 at the concentration of 10 μM or with SB203580 in combination with bFGF at the dose of 133 pg/ml. Cells for immunofluorescent studies were fixed with 70% ethanol and stained with antibodies to CcO subunit I. Results: When exposed to SB203580 or the combination of SB203580 and bFGF, marked changes were observed in the fibroblast culture: in both cases there was intensive collagen destruction; attached fibroblasts rounded and detached from the substrate. When exposed to SB203580, non-rounded cells started to vacuolate actively while vacuoles occupied the entire cytoplasm. Introduction of the p38 inhibitor into the culture of activated fibroblasts caused a more intensive cell detachment and collagen destruction. Moreover, the formation of large conglomerates containing several dozens of cells connected with collagen fibers was observed in the areas characterized by the highest cell density. Immunofluorescent staining made it possible to reveal a certain increase in the cell area occupied by CcO after fibroblasts exposure to SB203580 and a significant increase in the area of the enzyme distribution in the studied cells (more than 5-fold in comparison with the control group) when simultaneously adding SB203580 and bFGF. In addition, one-way ANOVA test demonstrated a statistically significant increase in the CcO fluorescent staining intensity in both cases. Conclusion: The analysis of the results indicates that SB203580, a p38 MAPK inhibitor, influences both peritoneal fibroblast morphology and the energy status of the cells under study increasing the amount of CcO, the terminal enzyme of the mitochondrial electron transport chain, in the cells, although no cell change to active proliferation or apoptosis was observed. Fibroblast culture stimulation by bFGF significantly enhances the effect of SB203580, which implies a greater OxPhos complex expression in case of impaired p38 MAPK signaling pathway ...

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Effect of p38 MAPK Inhibition on Apoptosis Marker Expression in the Process of Peritoneal Adhesion Formation

Cited by 4 publications

References 11 publications

Growth factors in the regulation of reparative response in the presence of peritoneal damage

Growth factors in the regulation of reparative response in the presence of peritoneal damage

Using Ki-67 Mitotic Activity Markers as a Predictor of the Progression of Adhesions in the Abdominal Cavity

Changes in Oxidative Phosphorylation Activity in Fibroblasts at p38 MAPK Pathway Inhibition

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