Metabolic reprogramming and Warburg effect in keloids

Sun, Hui

doi:10.1016/j.burns.2022.04.021

Cited by 2 publications

(1 citation statement)

References 3 publications

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“…However, there was a lack of effective keloid animal models, and purified cultured fibroblasts from keloid samples for in vitro experiments do not share the same status as fibroblasts in keloid tissue or nodules. 33 Thus, further studies to verify the effects of miR-133b-3p for keloid fibroblasts (eg, miRNA transfer experiment in vitro and ex vivo) are needed to better understand these mechanisms. 17 , 20 , 34 …”

Section: Discussionmentioning

confidence: 99%

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

Lee

Ito

Taniguchi

et al. 2023

Plastic and Reconstructive Surgery - Global Open

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Background: A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue. Methods: Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c). Results: Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue. Conclusions: The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids.

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Section: Discussionmentioning

confidence: 99%

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

Lee

Ito

Taniguchi

et al. 2023

Plastic and Reconstructive Surgery - Global Open

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Roles of MMP-2 and MMP-9 and their associated molecules in the pathogenesis of keloids: a comprehensive review

Wang,

Zheng,

Zhang

et al. 2024

Front. Pharmacol.

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Keloid scars (keloids), a prototypical form of aberrant scar tissue formation, continue to pose a significant therapeutic challenge within dermatology and plastic surgery due to suboptimal treatment outcomes. Gelatinases are a subgroup of matrix metalloproteinases (MMPs), a family of enzymes that play an important role in the degradation and remodeling of the ECM (a pivotal factor for keloids development). Gelatinases include gelatinase A (MMP-2) and gelatinase B (MMP-9). Since accumulating evidence has shown that gelatinases played a crucial role in the process of keloid formation, we summarized the current knowledge on the association between MMP-2 and MMP-9 expression and the pathological process of keloids through a comprehensive review. This review demonstrated that the interplay between MMP-2, MMP-9, and their regulators, such as TGF-β1/Smad, PI3K/AKT, and LncRNA-ZNF252P-AS1/miR-15b-5p/BTF3 signaling cascades, involved in the intricate balance governing ECM homeostasis, collectively driving the excessive collagen deposition and altered tissue architecture observed in keloids. In summary, this review consolidates the current understanding of MMP-2 and MMP-9 in keloid pathogenesis, shedding light on their intricate involvement in the dysregulated keloids processes. The potential for targeted therapeutic interventions presents promising opportunities for advancing keloid management strategies.

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Metabolic reprogramming and Warburg effect in keloids

Cited by 2 publications

References 3 publications

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

Roles of MMP-2 and MMP-9 and their associated molecules in the pathogenesis of keloids: a comprehensive review

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