Necrostatin‐1, RIP1/RIP3 inhibitor, relieves transforming growth factor β‐induced wound‐healing process in formation of hypertrophic scars

Lin, Pei-Ting; Xue, Xiaodong; Zhao, Zheng; Lu, Junyang; Xie, Peilin

doi:10.1111/jocd.13860

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…KD is characterized excessive collagen deposition due to an imbalance between the production and degradation of the ECM. 12 In the process of KD tissue proliferation, the synthesis of type I and III collagens increases from the translation stage to the protein synthesis stage. It has been suggested that a large number of fibroblasts activate type I and III procollagen mRNA expression in the endoplasmic reticulum to produce type I and III procollagens.…”

Section: Discussionmentioning

confidence: 99%

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Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF‐β1/SMAD signaling pathway

Luo

Wang

Yuan

et al. 2023

J of Cosmetic Dermatology

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Background: Keloid (KD) is a unique pathological fibroproliferative disease that seriously affects the appearance of patients. This study investigated the effect of oleanolic acid (OA) on the proliferation of keloid fibroblasts (KFs) and the expression of extracellular matrix (ECM)-related proteins. Methods:The proliferation of KFs was evaluated using an MTT assay. The effects of OA on intra-and extracellular levels of fibronectin (FN), procollagen I, matrix metalloproteinase-1 (MMP-1), and α-smooth muscle actin (α-SMA) were evaluated using Western blotting. To simulate the KD microenvironment, TGF-β1 was added to the serum-free culture medium, and KFs were incubated with TGF-β1 and OA for 24 h.The intra-and extracellular levels of the ECM-related proteins and the effect of OA on TGF-β1-induced phosphorylation of the SMAD2 and SMAD3 proteins were evaluated using Western blotting.Results: OA inhibited the proliferation of KFs in a concentration-and time-dependent manner. Furthermore, OA treatment of KFs reduced the intra-and extracellular levels of FN, procollagen I, and α-SMA and increased those of MMP-1. OA also reduced TGF-β1-induced increases in the intra-and extracellular levels of FN, procollagen I, and α-SMA and increased the levels of the MMP-1 protein. Additionally, OA significantly reduced TGF-β1-induced phosphorylation of SMAD2 and SMAD3 in KFs.Conclusions: OA inhibited KF proliferation and reduced ECM deposition through the TGF-β1/SMAD pathway, which suggests that OA may be an effective drug for the prevention and treatment of KD.

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Section: Discussionmentioning

confidence: 99%

“…KD is characterized by excessive collagen deposition due to an imbalance between the production and degradation of the ECM 12 . In the process of KD tissue proliferation, the synthesis of type I and III collagens increases from the translation stage to the protein synthesis stage.…”

Section: Discussionmentioning

confidence: 99%

Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF‐β1/SMAD signaling pathway

Luo

Wang

Yuan

et al. 2023

J of Cosmetic Dermatology

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“… 15 A recent investigation manifested that RIPK1 was overexpressed in human hypertrophic scar fibroblasts, and inhibition of RIPK1 by using its inhibitor Necrostatin-1 partially limited proliferation and migration of the hypertrophic scar fibroblasts. 30 An in vitro and in vivo exploration from Mou and colleagues also indicated that Necrostatin-1, inhibitor of RIPK1, weakened proliferative ability of pulmonary fibroblasts, suppressed the expression of collagen I, collagen IV, α-smooth muscle actin and fibronectin, decreased collagen deposition and ameliorated fibrosis of lung tissues. 31 Combined with our research, these findings suggested that RIPK1 might promote proliferation of KFs and increase extracellular matrix in keloid.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-23b-3p Ameliorates Scar-Like Phenotypes of Keloid Fibroblasts by Facilitating A20 Expression

Kuai¹,

Jian²

2022

CCID

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Purpose Accumulating evidence has reported that microRNAs (miRNAs) play a critical role in the mechanism of keloid formation, and recent research found that miR-23b-3p was upregulated in keloid fibroblasts (KFs). Herein, we explored the potential effect of miR-23b-3p on fibroblasts in keloid. Materials and Methods Clinical tissues, primary KFs and KEL FIB cells were used to detect the expression of miR-23b-3p by performing qRT-PCR. Gene knockdown was carried out to evaluate the molecular and biological changes of primary KFs and KEL FIB cells by conducting CCK-8 assay, flow cytometry and Western blot. The online databases and luciferase reporter assay were utilized to screen and identify the potential target of miR-23b-3p. Results Upregulation of miR-23b-3p was detected in keloid tissues, primary KFs and KF cell line KEL FIB cells, and inhibition of miR-23b-3p promoted apoptosis and suppressed proliferation and the expression of collagen I, collagen III and fibronectin of primary KFs and KEL FIB cells. Further investigation revealed that TNFAIP3 , the ubiquitin-editing enzyme A20, was the direct target of miR-23b-3p, and inhibition of miR-23b-3p promoted the expression of A20 in primary KFs and KEL FIB cells. The in vitro assays indicated that A20 suppression inhibited apoptosis and facilitated proliferation and the expression of collagen I, collagen III and fibronectin of miR-23b-3p inhibitor-transfected primary KFs and KEL FIB cells. Finally, we found that miR-23b-3p inhibitor reduced the expression of receptor interacting serine/threonine protein kinase 1 (RIPK1), which was partially reversed by A20 inhibition. Conclusion These findings suggested that inhibition of miR-23b-3p/A20/RIPK1 axis induced apoptosis, limited proliferation and decreased extracellular matrix of KFs, providing a potential therapeutic target for treatment of keloid.

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“…On the contrary, it is also documented that a variety of drugs can downregulate necroptosis including small molecule inhibitors, immunosuppressive drugs, traditional Chinese medicines drugs, and other agents. There were plenty of small molecule inhibitors used in the treatment of multiple diseases or research in healthy subjects such as Dabrafenib, 204 Carfilzomib, 205 Sorafenib, 206 Pazopanib, 207 Ponatinib, 208 ZYZ‐803, 209 Nec‐1, 210 GSK2982772, 211 GSK3145095, 212 NSA, 63 , 64 GSK074, 76 and GW806742X. 87 The immunosuppressive drug Cyclosporine A 213 and Rapamycin 214 were also used to downregulate necroptosis.…”

Section: Drugs and Agents That Regulate Necroptosismentioning

confidence: 99%

The role of necroptosis in disease and treatment

Liu

Xie

Ren

et al. 2021

MedComm

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Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor‐interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain‐like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.

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Necrostatin‐1, RIP1/RIP3 inhibitor, relieves transforming growth factor β‐induced wound‐healing process in formation of hypertrophic scars

Cited by 8 publications

References 24 publications

Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF‐β1/SMAD signaling pathway

Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF‐β1/SMAD signaling pathway

Inhibition of miR-23b-3p Ameliorates Scar-Like Phenotypes of Keloid Fibroblasts by Facilitating A20 Expression

The role of necroptosis in disease and treatment

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