p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

Truzzi, Francesca; Marconi, Alessandra; Atzei, Paola; Panza, Maria Cristina; Lotti, Roberta; Dallaglio, Katiuscia; Tiberio, Rossana; Palazzo, Elisabetta; Vaschieri, Cristina; Pincelli, Carlo

doi:10.1038/cdd.2010.162

Cited by 55 publications

(70 citation statements)

References 41 publications

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“…Although it is widely accepted that p75 has a pro‐apoptotic role in neural cells [Blochl and Blochl, ], few studies documenting the apoptotic aspects of p75 in epithelial cells have been reported. Recently, Truzzi et al [] demonstrated that the activation of p75 facilitates apoptosis in skin keratinocytes, supporting our finding of BDNF‐induced cleaved caspase‐3 expression and TUNEL‐positive apoptotic cells among gingival epithelial cells. Importantly, consistent with the present study, JNK phosphorylation caused by BDNF via p75 was responsible for the skin keratinocyte apoptosis.…”

Section: Discussionsupporting

confidence: 91%

Distinction Between Cell Proliferation and Apoptosis Signals Regulated by Brain‐Derived Neurotrophic Factor in Human Periodontal Ligament Cells and Gingival Epithelial Cells

Kashiwai

Kajiya

Matsuda

et al. 2015

J of Cellular Biochemistry

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Previously, we reported that brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration by inducing periodontal ligament cell proliferation in vivo. In addition, the down growth of gingival epithelial cells, which comprises a major obstacle to the regeneration, was not observed. However, the underlying molecular mechanism is still unclear. Therefore, this study aimed to investigate the effect of BDNF on cell proliferation and apoptosis in human periodontal ligament (HPL) cells and human gingival epithelial cells (OBA9 cells) and to explore the molecular mechanism in vitro. HPL cells dominantly expressed a BDNF receptor, TrkB, and BDNF increased cell proliferation and ERK phosphorylation. However, its proliferative effect was diminished by a MEK1/2 inhibitor (U0126) and TrkB siRNA transfection. Otherwise, OBA9 cells showed a higher expression level of p75, which is a pan-neurotrophin receptor, than that of HPL cells. BDNF facilitated not cell proliferation but cell apoptosis and JNK phosphorylation in OBA9 cells. A JNK inhibitor (SP600125) and p75 siRNA transfection attenuated the BDNF-induced cell apoptosis. Moreover, OBA9 cells pretreated with SP600125 or p75 siRNA showed cell proliferation by BDNF stimulation, though it was reduced by U0126 and TrkB siRNA. Interestingly, overexpression of p75 in HPL cells upregulated cell apoptosis and JNK phosphorylation by BDNF treatment. These results indicated that TrkB-ERK signaling regulates BDNF-induced cell proliferation, whereas p75-JNK signaling plays roles in cell apoptotic and cytostatic effect of BDNF. Overall, BDNF activates periodontal ligament cells proliferation and inhibits the gingival epithelial cells growth via the distinct pathway. J. Cell. Biochem. 117: 1543-1555, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 91%

Distinction Between Cell Proliferation and Apoptosis Signals Regulated by Brain‐Derived Neurotrophic Factor in Human Periodontal Ligament Cells and Gingival Epithelial Cells

Kashiwai

Kajiya

Matsuda

et al. 2015

J of Cellular Biochemistry

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“…CD271 was firstly isolated from a melanoma cell line and is expressed on neural crest cells from which melanocytes are derived (Kruger et al, 2002). It belongs to the TNF receptor superfamily and mediates apoptosis in different cell settings via its own signaling pathway (Kraemer et al, 2014;Truzzi et al, 2011;Blöchl and Blöch, 2007). The interaction of apoptosis related protein APR-1 with CD271 activate apoptosis in melanoma cells (Selimovic et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

CD271 Down-Regulation Promotes Melanoma Progression and Invasion in Three-Dimensional Models and in Zebrafish

Saltari

Truzzi

Quadri

et al. 2016

Journal of Investigative Dermatology

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CD271 is a neurotrophin receptor variably expressed in melanoma. Although contradictory data are reported on its role as a marker of tumor-initiating cells, little is known about its function in tumor progression. CD271 expression was higher in spheroids derived from freshly isolated cells of primary melanomas and in primary WM115 and WM793-B cell lines, and it decreased during progression to advanced stages in cells isolated from metastatic melanomas and in metastatic WM266-4 and 1205Lu cell lines. Moreover, CD271 was scarcely detected in the highly invasive spheroids (SKMEL28 and 1205Lu). CD271, originally expressed in the epidermis of skin reconstructs, disappeared when melanoma started to invade the dermis. SKMEL8 CD271(-) cells showed greater proliferation and invasiveness in vitro and were associated with a higher number of metastases in zebrafish compared with CD271(+) cells. CD271 silencing in WM115 induced a more aggressive phenotype in vitro and in vivo. On the contrary, CD271 overexpression in SKMEL28 cells reduced invasion in vitro, and CD271 overexpressing 1205Lu cells was associated with a lower percentage of metastases in zebrafish. A reduced cell-cell adhesion was also observed in the absence of CD271. Taken together, these results indicate that CD271 loss is critical for melanoma progression and metastasis.

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“…BDNF shows its effect by triggering keratinocyte apoptosis via p75NTR (26). Truzzi et al (26) observed that the apoptosis triggered by the BDNF and p75NTR interaction was significant in keratinocytes in the normal skin but not in psoriatic skin. In our study, the low BDNF infiltration levels in epidermis and dermis in psoriasis patients support these findings.…”

Section: Discussionmentioning

confidence: 99%

“…Autocrine NGF protects the cells from programmed cell death (26). The NGF levels were higher in the epidermis in psoriatic skin than in healthy skin and psoriatic skin without lesions (26).…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Role of Neurotrophins in the Psoriasis and Metabolic Syndrome Relationship

Bulur¹,

Erdoğan²,

Çiftçi³

et al. 2017

tdd

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ÖzAmaç: Psoriasis hastalarında ve sağlıklı kontrollerde serum ve deri örneklerinde beyin türevli nörotrofik faktör (BDNF), sinir büyüme faktörü (NGF), tümör nekroz faktör-α (TNF) ve interlökin-6 (IL) düzeylerini belirleyerek metabolik sendrom (MetS) ve psoriasis ilişkisinde nörotrofinlerin yerini değerlendirmeyi amaçladık. Yöntemler: Serum BDNF, NGF, TNF-α ve IL-6 düzeyleri ticari hazır ELISA kitleri ile değerlendirildi. BDNF, NGF, TNF-α ve IL-6 antikorları ile BDNF, NGF, TNF-α ve IL-6'nın derideki ekspresyon düzeyi belirlendi. Bulgular: MetS risk faktörlerinden herhangi birinin eşlik etmediği 39 psoriasis vulgaris hastası, MetS'nin eşlik ettiği 21 psoriasis vulgaris hastası ile 15 sağlıklı kontrol çalışmaya dahil edildi. BDNF'nin serum, epidermal ve dermal infiltrasyon düzeyi kontrol grubunda psoriasis hastalarına göre belirgin olarak yüksek saptandı (p=0,017; p=0,019; p=0,002). Serum NGF, TNF-α ve IL-6 düzeyleri açısından gruplar arasında farklılık saptanmaz iken (p˃0,05), psoriasis hastalarında epidermiste NGF'nin infiltrasyon düzeyi kontrol grubuna göre daha fazla olup istatistiksel olarak anlamlı fark tespit edildi (p=0,003). Psoriasis hasta grupları arasında ise serum BDNF düzeyi, epidermal ve dermal BDNF infiltrasyon düzeyi ve epidermal NGF infiltrasyon düzeyi ise benzerdi (p>0,05). Sonuç: Çalışmamızdaki sonuçlar nörotrofinlerin psoriasis patogenezindeki yerini desteklemektedir. Ancak çalışmamızda psoriasis grupları arasında serum ve doku BDNF, NGF düzeylerinin değişmemiş olması, psoriasis immünopatogenezinde nörotrofinlerin metabolik durumdan bağımsız olarak inflamatuvar süreç ile ilişkili olduğunu düşündürmüştür. Anahtar kelimeler: Beyin türevli nörotrofik faktör, sinir büyüme faktörü, nörotrofin, metabolik sendrom, psoriasis, immünopatogenez Objective: We aimed to evaluate the role of neurotrophins in relation to metabolic syndrome (MetS) and psoriasis by determining brain derived neurotrophic hormon (BDNF), nerve growth factor (NGF), tumor necrosis factor-α (TNF) and interleukin-6 (IL) levels in serum and skin samples of psoriasis patients and healthy controls. Methods: The BDNF, NGF, TNF-α and IL-6 levels were assessed using commercially available ELISA kits. The level of expression BDNF, NGF, TNF-α and IL-6 antibodies was determined by BDNF, NGF, TNF-α and IL-6 Antibodies. Results: Thirty nine psoriasis vulgaris patients without MetS risk factors, 21 patients with psoriasis vulgaris accompanied by MetS and 15 healthy controls were included in the study. The serum BDNF levels, epidermal and the dermal infiltration levels of BDNF were significantly higher in the control group than in the psoriasis patients (p=0.017, p=0.019, p=0.002). There was no difference between the groups in terms of serum NGF, TNF-α and IL-6 levels (p˃0.05), but the infiltration level of NGF in the epidermis was higher in the psoriasis patients than the control group and statistically significant difference was found (p=0.003). Serum BDNF levels, epidermal and dermal BDNF infiltration level and the epidermal NGF stainin...

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p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

Cited by 55 publications

References 41 publications

Distinction Between Cell Proliferation and Apoptosis Signals Regulated by Brain‐Derived Neurotrophic Factor in Human Periodontal Ligament Cells and Gingival Epithelial Cells

Distinction Between Cell Proliferation and Apoptosis Signals Regulated by Brain‐Derived Neurotrophic Factor in Human Periodontal Ligament Cells and Gingival Epithelial Cells

CD271 Down-Regulation Promotes Melanoma Progression and Invasion in Three-Dimensional Models and in Zebrafish

Evaluating the Role of Neurotrophins in the Psoriasis and Metabolic Syndrome Relationship

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