Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inﬂammation

Wang, Zhen; Zhou, Hong; Zheng, Huaping; Zhou, Xikun; Shen, Guobo; Teng, Xiu; Liu, Xiao; Zhang, Jun; Wei, Xiaoqiong; Hu, Zhonglan; Zeng, Fanlian; Hu, Yawen; Hu, Jing; Wang, Xiaoyan; Chen, Shuwen; Cheng, Juan; Zhang, Chen; Gui, Yi‐Yue; Zou, Song; Hao, Yan; Zhao, Qixiang; Wu, Wenling; Zhou, Yifan; Cui, Kaijun; Huang, Nongyu; Wei, Yuquan; Li, Wei; Li, Jiong

doi:10.1080/15548627.2020.1725381

Cited by 115 publications

(95 citation statements)

References 78 publications

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“…This LC3 increased expression was associated with increase expression of BECN1 and ATG5, suggesting that autophagy is activated in psoriatic keratinocytes. 24 The difference in our findings from the aforementioned could be attributed to different antibodies used. LC3B was used in the current study, while LC3A/B, LC3A, LC3B were used in the other study.…”

Section: Discussioncontrasting

confidence: 66%

Assessment of the Effect of Metabolic Syndrome on the Autophagy Marker LC3 in Psoriasis Vulgaris Patients: A Cross-Sectional Study

Nada

Muhammad

Ahmed

et al. 2020

CCID

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Purpose Psoriasis vulgaris, one of the most prevalent chronic inflammatory skin diseases, is associated with metabolic syndrome (MetS). Autophagy, an intracellular degradation system is essential for cell survival and differentiation, and its dysfunction may contribute to metabolic diseases. A cross-sectional study was conducted on 38 psoriasis vulgaris patients and 16 healthy control subjects to 1) Assess immunohistochemical (IHC) expression of microtubule-associated protein light chain 3 (LC3); 2) Evaluate the relationship between Psoriasis Area Severity Index (PASI) score, and LC3 expression. Patients and Methods PASI score was evaluated for all psoriasis patients. Lipid profile, blood sugar, and CRP were done for all patients and controls. A punch biopsy was taken from lesional and perilesional skin of psoriasis patients and normal skin of the controls. Tissue sections were prepared. IHC LC3 staining was done and evaluated. Results LC3 was nearly absent, in the epidermis of the lesional skin of psoriasis while it was strong among control (p=0.001). LC3 expression in the lesional skin of psoriasis vulgaris was lower than its expression in perilesional (p=0.001). However, LC3 expression was not significantly changed with PASI or the presence/absence of MetS. Conclusion A potential link between psoriasis vulgaris and autophagy as assessed by LC3 could be present. LC3 was down-regulated in psoriasis lesions than in normal skin. However, its expression did not change with PASI or MetS. An autophagy enhancer might be used as a possible therapeutic target in psoriasis vulgaris patients.

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Section: Discussioncontrasting

confidence: 66%

Assessment of the Effect of Metabolic Syndrome on the Autophagy Marker LC3 in Psoriasis Vulgaris Patients: A Cross-Sectional Study

Nada

Muhammad

Ahmed

et al. 2020

CCID

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“…In addition to IL1β, several proteins relying on autophagic machinery for secretion have been identified [97]. A leaderless protein whose release is prompted by inflammatory stimuli is the High-mobility group protein B1 (HMGB1) nuclear protein [98], that acts as a Damage Associated Molecular Pattern (DAMP) and whose autophagy-dependent secretion by keratinocytes plays a pivotal role in psoriatic skin inflammation [99]. Another relevant protein released by secretory autophagy is TGF-β1, which was demonstrated to be secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators [100].…”

Section: Non Degradative Function Of Autophagy: Secretory Autophagymentioning

confidence: 99%

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Buratta

Tancini

Sagini

et al. 2020

IJMS

285

204

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Beyond the consolidated role in degrading and recycling cellular waste, the autophagic-and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic-and endo-lysosomal systems, evaluating their implication in health and disease.

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“…It has been very recently described that miR-9-5p protects against inflammation through the inhibition of NF-κB [27,28]. Mir-9-5p also regulates the expression of ATG5 (Autophagy related 5) [29] and its overexpression in psoriatic skin has been recently reported [30]. Moreover, the keratinocyte-specific ablation of ATG5 ameliorated imiquimod-induced skin lesions in mice accompanied by a reduction in the number of IL-17A producing cells [30], highlighting the role of this target in psoriasis.…”

Section: Discussionmentioning

confidence: 95%

“…Mir-9-5p also regulates the expression of ATG5 (Autophagy related 5) [29] and its overexpression in psoriatic skin has been recently reported [30]. Moreover, the keratinocyte-specific ablation of ATG5 ameliorated imiquimod-induced skin lesions in mice accompanied by a reduction in the number of IL-17A producing cells [30], highlighting the role of this target in psoriasis. On the other hand, downregulation of miR-133a has been detected in asthma and its upregulation is able to ameliorate airway remodeling through PI3K/AKT/mTOR signaling pathways by targeting IGFR1 (insulin-like growth factor I receptor [31].…”

Section: Discussionmentioning

confidence: 96%

Expression of miR-135b in Psoriatic Skin and Its Association with Disease Improvement

Chicharro

Rodríguez‐Jiménez

Llamas‐Velasco

et al. 2020

Cells

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miRNAs have been associated with psoriasis since just over a decade. However, we are far from a complete understanding of their role during the development of this disease. Our objective was to characterize the cutaneous expression of miRNAs not previously described in psoriasis, the changes induced following the treatment with biologicals and their association with disease improvement. Next generation sequencing was performed from five skin samples from psoriasis patients (lesional and non-lesional skin) and five controls, and from this cohort, 12 microRNAs were selected to be analyzed in skin samples from 44 patients with plaque psoriasis. In 15 patients, an additional sample was obtained after three months of biological treatment. MiR-9-5p, miR-133a-3p and miR-375 were downregulated in the lesional skin of psoriasis patients. After treatment, expression of miR-133a-3p, miR-375, miR-378a and miR-135b in residual lesions returned towards the levels observed in non-lesional skin. The decrease in miR-135b levels after treatment with biologics was associated with both the improvement of patients evaluated through Psoriasis Area and Severity Index score and the decrease in local inflammatory response. Moreover, basal expression of miR-135b along with age was associated with the improvement of psoriasis, suggesting its possible usefulness as a prognostic biomarker.

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Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inﬂammation

Cited by 115 publications

References 78 publications

Assessment of the Effect of Metabolic Syndrome on the Autophagy Marker LC3 in Psoriasis Vulgaris Patients: A Cross-Sectional Study

Assessment of the Effect of Metabolic Syndrome on the Autophagy Marker LC3 in Psoriasis Vulgaris Patients: A Cross-Sectional Study

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Expression of miR-135b in Psoriatic Skin and Its Association with Disease Improvement

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