Sumoylation enhances the activity of the TGF-β/SMAD and HIF-1 signaling pathways in keloids

Lin, Xiaohu; Wang, Yuming; Jiang, Yan; Xu, Ming; Pang, Qiuxiang; Sun, Jiaqi; Yu, Yijia; Shen, Zeren; Li, Rui; Xu, Jinghong

doi:10.1016/j.lfs.2020.117859

Cited by 26 publications

(22 citation statements)

References 43 publications

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“…Firstly, keloid-derived fibroblasts served as the main cellular components in keloid skin tissue play a pivotal role in modulating the synthesis and remodeling of ECM and wound scar healing after burns, trauma, and surgery [6]. It is worth noting that the continuous transformation and invasive growth of fibroblasts into myofibroblasts is beyond the confines of the original wound, reflecting the characteristics of benign skin tumors of keloid [7].…”

Section: Epigenetic Mechanisms With Histopathologymentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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Section: Epigenetic Mechanisms With Histopathologymentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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“…It is not surprising that the effect of SUMOylation on various proteins differs. Although many studies show that SUMO modification promotes TGF-β-induced fibrosis [143], some proteins, such as Smad4, MEK, TAB2, PTEN, PI3K, c-Jun and SNIP, exhibit inhibitory effects on TGF-β signalling after being SUMOylated. We attempted herein to explain observations using the MAPK family as an example.…”

Section: Discussion and Outlookmentioning

confidence: 99%

Regulation of transforming growth factor-β signalling by SUMOylation and its role in fibrosis

et al. 2021

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Fibrosis is an abnormal healing process that only repairs the structure of an organ after injury and does not address damaged functions. The pathogenesis of fibrosis is multifactorial and highly complex; numerous signalling pathways are involved in this process, with the transforming growth factor-β (TGF-β) signalling pathway playing a central role. TGF-β regulates the generation of myofibroblasts and the epithelial–mesenchymal transition by regulating transcription and translation of downstream genes and precisely regulating fibrogenesis. The TGF-β signalling pathway can be modulated by various post-translational modifications, of which SUMOylation has been shown to play a key role. In this review, we focus on the function of SUMOylation in canonical and non-canonical TGF-β signalling and its role in fibrosis, providing promising therapeutic strategies for fibrosis.

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“…In contrast, TGF-β-secreted factors can indirectly contribute to fibrosis through signaling pathways in an inflammatory microenvironment ( Hahn et al, 2016 ). In addition, pro-inflammatory factors such as interleukin (IL)-1α, IL-1β, and IL-8, CKLF-1, and COX-1 are upregulated in the keloid tissue, suggesting that in patients with keloids, pro-inflammatory genes in the skin are sensitive to trauma, which in turn may promote chronic inflammation and lead to excessive keloid growth ( Abdou et al, 2014 ; Lin et al, 2020 ; Wu et al, 2020 ).…”

Section: Keloid Pathogenesis Studymentioning

confidence: 99%

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

et al. 2022

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Keloids are fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin and are characterized by excessive extracellular matrix (ECM) synthesis and deposition, which results in excessive collagen disorders and calcinosis, increasing the remodeling and stiffness of keloid matrix. The pathogenesis of keloid is very complex, and may include changes in cell function, genetics, inflammation, and other factors. In this review, we aim to discuss the role of biomechanical factors in keloid formation. Mechanical stimulation can lead to excessive proliferation of wound fibroblasts, deposition of ECM, secretion of more pro-fibrosis factors, and continuous increase of keloid matrix stiffness. Matrix mechanics resulting from increased matrix stiffness further activates the fibrotic phenotype of keloid fibroblasts, thus forming a loop that continuously invades the surrounding normal tissue. In this process, mechanical force is one of the initial factors of keloid formation, and matrix mechanics leads to further keloid development. Next, we summarized the mechanotransduction pathways involved in the formation of keloids, such as TGF-β/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway. Finally, some potential biomechanics-based therapeutic concepts and strategies are described in detail. Taken together, these findings underscore the importance of biomechanical factors in the formation and progression of keloids and highlight their regulatory value. These findings may help facilitate the development of pharmacological interventions that can ultimately prevent and reduce keloid formation and progression.

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Sumoylation enhances the activity of the TGF-β/SMAD and HIF-1 signaling pathways in keloids

Cited by 26 publications

References 43 publications

Epigenetic modification mechanisms involved in keloid: current status and prospect

Epigenetic modification mechanisms involved in keloid: current status and prospect

Regulation of transforming growth factor-β signalling by SUMOylation and its role in fibrosis

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

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