PGRN Suppresses Inflammation and Promotes Autophagy in Keratinocytes Through the Wnt/β-Catenin Signaling Pathway

Tian, Rong; Li, You; Yao, Xu

doi:10.1007/s10753-016-0370-y

Cited by 52 publications

(37 citation statements)

References 39 publications

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“…In the current study, there was a significant stepwise upregulation of PGRN from normal skin of controls passing to perilesional and ended by lesional psoriatic skin in psoriasis patients. In agreement with our results, Tian et al reported that PGRN was significantly upregulated in lesional skin from psoriasis patients (n = 11) than perilesional skin (n = 8) and biopsies from healthy individuals (n = 9). Additionally, Huang et al demonstrated that PGRN protein and mRNA expression levels were significantly higher in psoriatic lesions than controls.…”

Section: Discussionsupporting

confidence: 93%

“…In the present study, progranulin was negatively correlated with β‐catenin expression in perilesional and lesional psoriatic skin, suggesting that pro‐inflammatory effect of progranulin in psoriasis may be mediate through decreasing β‐catenin expression in psoriasis. Parallel to our observation, Tian et al through their in vitro study using culture HaCat cells reported that PGRN inhibited the activity of β‐catenin signaling pathway, and its target genes cyclin D1 and c‐myc. Also, in degenerative arthritis, PGRN inhibited the activation of β‐catenin signaling in chondrocytes …”

Section: Discussionsupporting

confidence: 86%

“…Progranulin is highly expressed in skin diseases and plays an important role in inflammation response and autophagy that could be mediated through Wnt/β‐catenin pathway . However, the function of PGRN in immune system and autophagy in psoriasis has not been clearly identified.…”

Section: Introductionmentioning

confidence: 99%

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Progranulin and beta‐catenin in psoriasis: An immunohistochemical study

Farag

Shoaib

Samaka

et al. 2019

J of Cosmetic Dermatology

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Background/Objectives Progranulin (PGRN) is a secreted glycoprotein that was investigated in many skin diseases. It plays an important role in inflammatory response and autophagy which could be mediated through Wnt/β‐catenin pathway. However, the role of PGRN in pathogenesis of psoriasis has not been clearly well‐known. Therefore, we aimed by this study to investigate the possible role of progranulin in psoriasis pathogenesis through evaluation of its immunohistochemical expression in lesional and perilesional skin of psoriasis patients and to investigate if its hypothesized role is mediated through β‐catenin or not. Methods This case‐control study was carried out on 37 patients presented with variable degrees of psoriasis vulgaris severity vs 37 age and sex‐matched apparently healthy volunteers. Psoriasis area and severity index (PASI) score was used to evaluate the severity of psoriasis. From all cases (lesional and perilesional) and controls, skin biopsies were taken for histopathological and immunohistochemical evaluation of PGRN and β‐catenin. Results There was a significant stepwise upregulation of PGRN from controls (76.2 ± 11.9) to perilesional (178.7 ± 11.8) and lesional (242.7 ± 12.7) psoriatic skin (P < 0.001). PGRN expression was significantly correlated with psoriasis severity (r = 0.61; P < 0.001). β‐catenin showed a significant stepwise downregulation from control (210.0 ± 19.3) to perilesional (131.4 ± 9.2) and lesional (97.3 ± 11.5) psoriatic skin(P < 0.001). There was a significant negative correlation between PGRN and β‐catenin expression in psoriatic skin (P < 0.001). Conclusions Progranulin has a pro‐inflammatory effect in the psoriasis pathogenesis, which could be mediated through a decreasing β‐catenin expression in psoriasis. PGRN may be used as a target for immunotherapy in psoriasis management program.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 86%

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Progranulin and beta‐catenin in psoriasis: An immunohistochemical study

Farag

Shoaib

Samaka

et al. 2019

J of Cosmetic Dermatology

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“…Autophagy is a highly regulated process that is involved in many pathophysiological situations, including cerebral ischemia/reperfusion injury . Autophagy has been considered a double‐edged sword with prosurvival or prodeath potential in cerebral ischemia/reperfusion injury .…”

Section: Discussionmentioning

confidence: 99%

Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats

et al. 2017

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Ischemic stroke is a leading cause of death and disability worldwide, and autophagy may be involved in the pathological process of cerebral ischemia/reperfusion injury. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with protective effects against multiple diseases. Here, we tested the effect of H2S on cerebral ischemia/reperfusion injury in rats. Sodium hydrosulfide (NaHS), an H2S donor, improved neurological function and reduced the size of the infarcts induced by transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats. NaHS treatment reduced the lactate dehydrogenase (LDH) activity in the serum (a marker of cellular membrane integrity) and the expression of cleaved caspase‐3 (a marker for apoptosis) in the brains of MCAO rats. We also found that autophagy was overactivated in the brains of MCAO rats, as indicated by an increased ratio of LC3 II to I, decreased expression of p62, and transmission electron microscope detection. NaHS treatment significantly inhibited the autophagic activity in the brains of MCAO rats. Furthermore, PC12 cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to mimic MCAO in vitro. We found that NaHS treatment reduced cellular injury and suppressed overactivated autophagy induced by OGD/R in PC12 cells. An autophagy stimulator (rapamycin) eliminated the protective effect of NaHS against LDH release and caspase‐3 activity induced by OGD/R in PC12 cells. An autophagy inhibitor (3‐methyladenine, 3‐MA) also reduced the cellular injury induced by OGD/R in PC12 cells. In conclusion, the results indicate that overactivated autophagy accelerates cellular injury after MCAO in rats and that exogenous H2S attenuates cerebral ischemia/reperfusion injury via suppressing overactivated autophagy in rats.

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“…* P<0.05 and *** P<0.001. miR, microRNA. the overexpression of progranulin inhibited TNF-α-induced inflammation in keratinocytes by positively mediating autophagy through the Wnt/β-catenin signaling pathway (25). More studies are required to elucidate the detailed role of β-catenin in the miR-24-mediated inhibition of autophagy.…”

Section: Discussionmentioning

confidence: 99%

β‑catenin regulates effects of miR‑24 on the viability and autophagy of glioma cells

Chen

et al. 2019

Exp Ther Med

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Mutations of the β-catenin gene are common in various cancer types. MicroRNA (miR)-24 suppresses gene expression during the cell cycle. However, the effects of miR-24 on the cell viability and autophagy of glioma cells, and how these biological processes are regulated by β-catenin are largely unclear. The current study aimed to investigate the role of β-catenin in regulating the effects of miR-24 on the cell viability and autophagy of glioma cells. The expression levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 were detected by immunohistochemistry and western blotting. Glioma C6 cells were transfected with miR-24 mimics, miR-24 inhibitors and negative control miRNAs. C6 cells transfected with miR-24 mimics or negative control miRNAs were treated with the β-catenin inhibitor, XAV-939. An MTT assay was utilized to evaluate the viability of C6 cells. The expression of miR-24 and mRNA expression of autophagy related 4a cysteine peptidase (ATG4A) were detected by quantitative polymerase chain reaction analysis. The protein expression of LC3B and Beclin1 decreased significantly in glioma tissue and glioma C6 cells compared with normal brain tissue. Compared with the negative control group, C6 cells transfected with miR-24 mimics exhibited significantly higher cell viability at 24 and 48 h, and those transfected with miR-24 inhibitors exhibited significantly lower cell viability at 48 h. XAV-939 decreased the stimulatory effects of miR-24 mimics on the viability of C6 cells. The expression of miR-24 significantly decreased and ATG4A mRNA significantly increased in C6 cells transfected with XAV-939 compared with those transfected with the negative control miRNA. XAV-939 attenuated the miR-24-induced decrease of the protein expression of LC3B and Beclin1, and decreased the stimulatory effects of miR-24 mimics on cell viability. In addition, XAV-939 attenuated the miR-24-induced decrease of autophagy marker expression by attenuating miR-24 expression and increasing ATG4A mRNA expression in glioma C6 cells. To the best of our knowledge, the present study is the first to demonstrate whether β-catenin regulates the intracellular effects of miR-24 on the viability and autophagy of glioma cells. The results also provide some mechanistic basis to the pharmaceutical targeting of WNT signaling in high grade glial tumors.

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PGRN Suppresses Inflammation and Promotes Autophagy in Keratinocytes Through the Wnt/β-Catenin Signaling Pathway

Cited by 52 publications

References 39 publications

Progranulin and beta‐catenin in psoriasis: An immunohistochemical study

Progranulin and beta‐catenin in psoriasis: An immunohistochemical study

Sodium hydrosulfide attenuates cerebral ischemia/reperfusion injury by suppressing overactivated autophagy in rats

β‑catenin regulates effects of miR‑24 on the viability and autophagy of glioma cells

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