Functions of the RIP kinase family members in the skin

Urwyler-Rösselet, Corinne; Tanghe, Giel; Devos, Michael; Hulpiau, Paco; Saeys, Yvan; Declercq, Wim

doi:10.1007/s00018-023-04917-2

Cited by 3 publications

(1 citation statement)

References 199 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is probable that proliferating and actively synthesizing cells in the transplant significantly reduce the levels of free oxygen radicals through the synthesis of antioxidant defense enzymes on the 6th day. Alternatively, an increase in the content of active caspases may play a role in suppressing the activity of RIP protein kinase, an initiator of necrosis in cells (Moriwaki & Chan, 2014;Urwyler-Rösselet et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

Kot,

Kurbanov

2023

Regul. Mech. Biosyst.

View full text Add to dashboard Cite

In the course of radiation therapy, normal cells surrounding the tumor are also irradiated. During and after irradiation, they undergo a series of structural and metabolic changes, which can lead to cell death or transformation. Therefore, when planning and conducting radiation therapy, the effects of radiation on normal cells are taken into account with the aim of predicting and further correcting post-radiation complications, including the development of radiation burns and ulcers. Radiation skin burns are characterized by a prolonged course of the wound healing process, which is accompanied by a sharp decrease in the number of viable cells in the affected tissue from the first hours of irradiation. The type of cell death can significantly impact the effectiveness of radiation therapy and post-radiation complication correction. Therefore, it is important to study the type of their death in irradiated three-dimensional culture on a model of irradiated dermal equivalent, which is widely used today for modeling biological processes. To detect the pathways of cell death, the levels of reactive oxygen species, cell viability, number of cells undergoing autophagy, apoptosis, and necrosis, the content of active caspases 3, 8, and 9 was fluorometrically measured in the irradiated 3D cell culture by laser scanning confocal microscopy. It was determined that the transplantation of fibroblasts and keratinocytes into the irradiated dermal equivalent contributed to an increase in the overall viability of cells of the equivalent and led to a significant decrease in the concentration of free oxygen forms in the irradiated equivalent. Cells within the irradiated equivalent were not evenly distributed in terms of their quantity and viability, with an overall decrease in the cell count over time. A cluster of equivalent cells with significantly higher viability was formed around the transplant. At the same time, the fibroblasts of the transplant were found to be more resistant to the cytotoxic factors of the post-irradiation culture environment compared to keratinocytes. It was demonstrated that non-irradiated dermal equivalent cells predominantly undergo cell death through autophagy, irradiated equivalent cells primarily undergo necrosis, and after the introduction of the transplant, cell death predominantly occurs through apoptosis. In irradiated culture, both with and without transplantation, there is an increase in the content of effector caspase 3. Cells in irradiated culture undergo apoptosis through the mitochondrial mechanism (with a predominance of active caspase 9), while in irradiated culture with the introduction of the transplant, the receptor-mediated mechanism of apoptosis dominates (with a predominance of active caspase 8). The obtained results can be important for the development of new effective methods of therapy for radiation burns, chronic ulcers and wounds of various etiologies.

show abstract

Section: Discussionmentioning

confidence: 99%

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

Kot,

Kurbanov

2023

Regul. Mech. Biosyst.

View full text Add to dashboard Cite

show abstract

Unraveling the role of RIPKs in diabetic kidney disease and its therapeutic perspectives

Ambujakshan,

Sahu

2025

Biochemical Pharmacology

View full text Add to dashboard Cite

RIPK4 Downregulation Reduces ABCG2 Expression, Increasing BRAF-Mutated Melanoma Cell Susceptibility to Cisplatin- and Doxorubicin-Induced Apoptosis

Olajossy,

Wronski,

Madej

et al. 2024

Biomolecules

View full text Add to dashboard Cite

Melanoma cells remain resistant to chemotherapy with cisplatin (CisPt) and doxorubicin (DOX). The abnormal expression of Receptor-Interacting Protein Kinase 4 (RIPK4) in certain melanomas contributes to tumour growth through the NFκB and Wnt/β-catenin signalling pathways, which are known to regulate chemoresistance and recurrence. Despite this, the role of RIPK4 in response to chemotherapeutics in melanoma has not been reported. In this study, we examined how the downregulation and overexpression of RIPK4 affect the sensitivity of BRAF-mutated melanoma cells (A375 and WM266.4) to CisPt and DOX along with determining the underlying mechanism. Using two RIPK4 silencing methods (siRNA and CRISPR/Cas9) and overexpression (dCas9-VPR), we assessed CisPt and DOX-induced apoptosis using caspase 3/7 activity, annexin V/7AAD staining, and FASC analysis. In addition, qRT-PCR and Western blotting were used to detect apoptosis-related genes and proteins such as cleaved PARP, p53, and cyclin D1. We demonstrated that the overexpression of RIPK4 inhibits, while its downregulation enhances, CisPt- or DOX-induced apoptosis in melanoma cells. The effects of downregulation are similar to those observed with pre-incubation with cyclosporin A, an ABCG2 inhibitor. Additionally, our findings provide preliminary evidence of crosstalk between RIPK4, BIRC3, and ABCG2. The results of these studies suggest the involvement of RIPK4 in the observed resistance to CisPt or DOX.

show abstract

Functions of the RIP kinase family members in the skin

Cited by 3 publications

References 199 publications

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

Unraveling the role of RIPKs in diabetic kidney disease and its therapeutic perspectives

RIPK4 Downregulation Reduces ABCG2 Expression, Increasing BRAF-Mutated Melanoma Cell Susceptibility to Cisplatin- and Doxorubicin-Induced Apoptosis

Contact Info

Product

Resources

About