Elevated SIRT3 Parkin-dependently activates cell mitophagy to ameliorate TNF-α-induced psoriasis-related phenotypes in HaCaT cells through deacetylating FOXO3a for its activation

Ma, Yanli; Wang, Yu; Li, Yuzhen

doi:10.1007/s00403-022-02453-w

Cited by 8 publications

(12 citation statements)

References 54 publications

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“…This was achieved through the activation of the FOXO3a/Parkin signaling pathway, prompting cellular mitophagy. 12 Theacrine also shows…”

Section: Discussionmentioning

confidence: 93%

“…Notably, an increased expression of SIRT3 was shown to ameliorate psoriasis‐like phenotypes. This was achieved through the activation of the FOXO3a/Parkin signaling pathway, prompting cellular mitophagy 12 . Theacrine also shows potential in averting Parkinson's disease via activating SIRT3, which in turn mitigates oxidative nerve cell damage and apoptosis stemming from mitochondrial dysfunction 9 .…”

Section: Discussionmentioning

confidence: 99%

“…11 Notably, an increased expression of SIRT3 was shown to ameliorate psoriasislike phenotypes, which was achieved through the activation of the FOXO3a/Parkin signaling pathway, prompting cellular mitophagy. 12 However, the potential role of theacrine in psoriasis remains unexplored, and its mechanisms are yet to be elucidated. In this study, IMQ-induced psoriasis-like model in mice was established to elucidate that theacrine alleviates skin damage through the modulation of SIRT3/FOXO3a/Parkin pathway.…”

Section: Introductionmentioning

confidence: 99%

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Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway

Li,

Yan,

Yuan

et al. 2024

Int J of Rheum Dis

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BackgroundPsoriasis, a common chronic inflammatory skin condition, impacts around 2%–3% of the global population. Theacrine is recognized for its potential anti‐inflammatory and antioxidant properties. However, the role of theacrine in psoriasis remains unclear.PurposesTo investigate the effects of theacrine on psoriasis and explore the underlying signaling pathways.MethodsFor imiquimod (IMQ)‐induced Psoriasis‐like mice, the psoriatic inflammation was monitored using Psoriasis Area and Severity Index (PASI). The skin damage was observed using Hematoxylin and Eosin staining. The KI67 and CD4 in skin tissues were assessed using Immunohistochemistry analysis. Western blots were performed to evaluate the expression of Keratin 1 (KRT1), KRT6, LC3, P62, Beclin1, T‐bet, GATA3, RAR‐related orphan receptor (ROR)‐γt, Sirtuin‐3 (SIRT3), Forkhead Box O3a (FOXO3a) and Parkin. Additionally, LC3B expression was analyzed using an immunofluorescent assay, while flow cytometry was performed to analyze the percentage of Th17, Th1, and Th2 positive cells in skin‐draining lymph node.ResultsTheacrine improved skin condition by reducing hyperkeratosis and acanthosis, lowering PASI scores, and decreasing KI67‐positive cells. Theacrine also modulated keratin expression, elevating KRT1 while reducing KRT6 levels. Theacrine enhanced autophagy indicated by an increased LC3‐II/LC3‐I ratio and Beclin1, while reduced P62 levels. Additionally, Theacrine reduced CD4‐positive cells and suppressed Th17 and Th1 cell activation. Theacrine activated the FOXO3a/Parkin pathway by upregulating SIRT3 expression, and down‐regulation of SIRT3 counteracted theacrine's effects in psoriasis‐like mice.ConclusionTheacrine inhibits skin damage, promotes autophagy, and mediates inflammation in IMQ‐induced psoriasis mice via upregulating SIRT3 to activate FOXO3a/Parkin pathway, positioning theacrine as a candidate for psoriasis treatment.

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“…This was achieved through the activation of the FOXO3a/Parkin signaling pathway, prompting cellular mitophagy. 12 Theacrine also shows…”

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway

Li,

Yan,

Yuan

et al. 2024

Int J of Rheum Dis

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“…Recently, there have been multiple publications related to other skin pathologies in which sirtuin alteration may have clinically relevant dermatological applications ( 146 – 152 ). For example, resveratrol and its analogs resveratryl triacetate (RTA) and resveratryl triglycolate (RTG) have been tested in multiple clinical studies.…”

Section: Wound Healingmentioning

confidence: 99%

“…Psoriasis is another chronic inflammatory disease mediated through the activation of T cells which stimulate the proliferation of keratinocyte. Applications of sirtuins in psoriasis have been extensively studied ( 149 , 151 , 157 – 160 ). In a recent study D’Amico and colleagues, took punch biopsies from 6 untreated female patients affected with chronic plaque psoriasis.…”

Section: Wound Healingmentioning

confidence: 99%

The role of sirtuins in dermal fibroblast function

et al. 2023

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The sirtuins are a family of seven proteins that perform a variety of dermatological functions and help maintain both the structure and function of the skin. More specifically, the sirtuins have been shown to be altered in multiple dermal cell types including dermal fibroblasts. The functions of dermal fibroblasts are extensive, and include playing a significant role in wound healing as well as helping to maintain the integrity of the skin. As dermal fibroblasts age, they can undergo a state of permanent cell cycle arrest, known as cellular senescence. This senescent process can occur as a result of various stressors, including oxidative stress, ultraviolet radiation -induced stress, and replicative stress. In recent years, there has been a growing interest in both enhancing the cutaneous fibroblast’s ability to facilitate wound healing and altering fibroblast cellular senescence. Thus, in this review, we examine the relationship between sirtuin signaling and dermal fibroblasts to understand how this family of proteins may modulate skin conditions ranging from the wound healing process to photocarcinogenesis associated with fibroblast senescence. Additionally, we offer supporting data from experiments examining the relationship between fibroblast senescence and sirtuin levels in an oxidative stress model indicating that senescent dermal fibroblasts exhibit diminished sirtuin levels. Furthermore, we survey the research on the role of sirtuins in specific dermatological disease states that where dermal fibroblast function has been implicated. Finally, we conclude with outlining potential clinical applications of sirtuins in dermatology. In sum, we find that the literature on the involvement of sirtuins in dermal fibroblasts is limited, with research still in its early stages. Nevertheless, intriguing preliminary findings merit additional investigation into the clinical implications of sirtuins in dermatology.

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Proteomic identification of exosomes derived from psoriasis cells using data-independent acquisition mass spectrometry

Zhang,

2024

Arch Dermatol Res

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Elevated SIRT3 Parkin-dependently activates cell mitophagy to ameliorate TNF-α-induced psoriasis-related phenotypes in HaCaT cells through deacetylating FOXO3a for its activation

Cited by 8 publications

References 54 publications

Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway

Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway

The role of sirtuins in dermal fibroblast function

Proteomic identification of exosomes derived from psoriasis cells using data-independent acquisition mass spectrometry

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