Neuropeptide Y receptor 1 is expressed by B and T lymphocytes and mast cells in infantile haemangiomas

Tan, Elysia M S; Blackwell, Max G.; Dunne, Jonathan C.; Marsh, Reginald; Tan, Swee T.; Itinteang, Tinte

doi:10.1111/apa.13684

Cited by 12 publications

(13 citation statements)

References 15 publications

(20 reference statements)

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“…Like VPAC and PACAP receptors, NPY receptors, especially the Y1 subtype have been detected on almost every type of immune cell so far [ 171 , 172 ]. The aforementioned review highlighted the role of NPY in numerous inflammatory conditions like inflammatory bowel syndrome, ulcerative colitis, liver cirrhosis, asthma and atopic dermatitis, as well as autoimmune conditions including diabetes type I, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.…”

Section: Effects Of the Neuroendocrine Systemmentioning

confidence: 99%

Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

Grässel

2018

IJMS

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Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropin (ACTH) and β-endorphin (β-ED), and sympathetic neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY). Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs. In particular, α-MSH, ACTH and specific melanocortin-receptor (MCR) agonists appear to have promising anti-inflammatory actions demonstrated in animal models of experimentally induced arthritis and osteoarthritis (OA). Sympathetic neuropeptides have obtained increasing attention as they have crucial trophic effects that are critical for joint tissue and bone homeostasis. VIP and NPY are implicated in direct and indirect activation of several anabolic signaling pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase-activating polypeptide (PACAP) proved to be chondroprotective and, thus, might be a novel target in OA. Taken together, it appears more and more likely that the anabolic effects of these neuroendocrine peptides or their respective receptor agonists/antagonists may be exploited for the treatment of patients with inflammatory and degenerative joint diseases in the future.

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Section: Effects Of the Neuroendocrine Systemmentioning

confidence: 99%

Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

Grässel

2018

IJMS

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“…One snap-frozen proliferating and one involuted IH tissue samples from the original cohort of patients used for DAB IHC staining were used for Western blotting (WB). These tissue samples were processed as previously described ( 3 ) and transferred to nitrocellulose membranes (Thermo Scientific) using an iBlot 2 (Thermo Scientific). The membranes were blocked for 90 min at 4°C in 1x iBind™ Flex Solution (Thermo Scientific) and probed using an iBind™ Flex device (Thermo Scientific) with the following primary antibodies: pSTAT1 (1:1,000; cat# 9167, Cell Signaling Technology, Danvers, MA, USA), pSTAT3 (1:1,000; cat# 9145, Cell Signaling Technology), pSTAT5 (1:1000; cat# 9314, Cell Signaling Technology) and β-actin (1:2,000; cat# ab8226, Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

“…The membranes were blocked for 90 min at 4°C in 1x iBind™ Flex Solution (Thermo Scientific) and probed using an iBind™ Flex device (Thermo Scientific) with the following primary antibodies: pSTAT1 (1:1,000; cat# 9167, Cell Signaling Technology, Danvers, MA, USA), pSTAT3 (1:1,000; cat# 9145, Cell Signaling Technology), pSTAT5 (1:1000; cat# 9314, Cell Signaling Technology) and β-actin (1:2,000; cat# ab8226, Thermo Scientific). Detection and imaging of the blots were undertaken as routinely done in our laboratory ( 3 ). Human tonsil, mouse lung, and human liver total protein extracts were used as the positive controls for pSTAT1, pSTAT3, and pSTAT5, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Infantile hemangioma (IH), the most common tumor of infancy, affects up to 10% of infants with a predilection for female, Caucasian and premature infants ( 1 – 3 ). It typically undergoes rapid growth during infancy followed by a spontaneous gradual involution over 1–10 years, often leaving a fibro-fatty residuum ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…STAT3 is a key mediator of pluripotent cell maintenance and is a regulator of the NANOG-OCT4 pathway ( 14 ). We have previously shown the expression of the non-phosphorylated form of STAT3 on the endothelium and cells within the interstitium of proliferating IH, inferring its role in the stem cells within proliferating IH, although the localization of the phosphorylated/activated form of this transcription factor remains to be determined ( 3 ). STAT5 acts as a downstream messenger of EPOR in both primitive and definitive erythropoiesis and its absence is embryonically fatal ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylated Forms of STAT1, STAT3 and STAT5 Are Expressed in Proliferating but Not Involuted Infantile Hemangioma

et al. 2018

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We have recently demonstrated the expression of embryonic stem cell markers on the endothelium of infantile hemangioma, a functional hemogenic endothelium with the capacity for primitive erythropoiesis in vitro. Despite recent work characterizing stem cells within proliferating infantile hemangioma, the expression of STAT proteins, well documented for their roles in stem cell signaling, has not been investigated. 3,3-Diaminobenzidine and immunofluorescence immunohistochemical staining revealed expression of pSTAT1, pSTAT3 and pSTAT5 in proliferating infantile hemangioma samples with the strongest expression of pSTAT3. There was reduced expression of these pSTAT proteins in the involuted infantile hemangioma samples. Western blotting confirmed the identification of all these three proteins in proliferating infantile hemangioma. It is therefore not surprising that the phosphorylated/activated forms of these proteins are relatively abundantly expressed in proliferating, in comparison to involuted infantile hemangioma samples. We speculate that the reduced STAT activation, as infantile hemangioma involutes, is a reflection of the depletion of the abundant stem cells within proliferating infantile hemangioma, as the lesion involutes.

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Endogenous peptides profiles of human infantile hemangioma tissue and their clinical significance for treatment

Chen

et al. 2018

J of Cellular Biochemistry

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Endogenous peptides play crucial roles in various biological processes. Their effects on the pathogenesis of human infantile hemangioma remains poorly understood. In this study, we construct a comparative peptidomic profiling between human infantile hemangioma tissue and matched normal skin using liquid chromatography-tandem mass spectrometry. A total of 192 peptides were significantly differentially expressed in human infantile hemangioma tissue, with 182 upregulated, and 10 downregulated peptides between infantile hemangioma tissue and matched normal skin. Performing bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis), we found that precursor proteins of these differentially expressed peptides correlate with metabolic process, biological regulation, binding, catalytic activity, and pathways in cancer occurring during pathological changes of infantile hemangioma. Furthermore, 89 differentially expressed peptides shared homology with antimicrobial peptides and 13 matched known immunomodulatory peptides based on prediction database. In conclusion, our results reveal significantly altered expression profiles of peptides in human infantile hemangioma tissue. These peptides may participate in the etiology of infantile hemangioma and provide beneficial scheme for clinical treatments.

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Neuropeptide Y receptor 1 is expressed by B and T lymphocytes and mast cells in infantile haemangiomas

Abstract: NPYR1, but not NPYR2, was present in IHs. The localisation of NPYR1 to B and T lymphocytes and mast cells suggests its role in the biology of IHs. The demonstration of NPY on the NPYR1 cells, without active transcription, suggests that NPY was not being produced within IHs.

Cited by 12 publications

References 15 publications

Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

Phosphorylated Forms of STAT1, STAT3 and STAT5 Are Expressed in Proliferating but Not Involuted Infantile Hemangioma

Endogenous peptides profiles of human infantile hemangioma tissue and their clinical significance for treatment

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