Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: A special reference to the nested gene LYNX1

Moriwaki, Yuji; Takada, Kiyoko; Tsuji, Shoutaro; Kawashima, Koichiro; Misawa, Hidemi

doi:10.1016/j.intimp.2015.05.030

Cited by 15 publications

(16 citation statements)

References 17 publications

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“…SLURPs influence the healing process of dermal and mucosal wounds 19 , and they demonstrate anti-inflammatory effects on human intestinal epithelial cells and immunocytes 20 . In addition, SLURP-2 expression in human keratinocytes is regulated by cytokines 21 . In accordance with their proposed role, SLURPs participate in the development of several pathologies.…”

mentioning

confidence: 99%

Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors

Lyukmanova

Shulepko

Шенкарев

et al. 2016

Sci Rep

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Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and differentiation of epithelial cells. Previously, the auto/paracrine activity of SLURP-2 was considered to be mediated via its interaction with the α3β2 subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic resonance spectroscopy revealed a ‘three-finger’ fold of SLURP-2 with a conserved β-structural core and three protruding loops. Affinity purification using cortical extracts revealed that SLURP-2 could interact with the α3, α4, α5, α7, β2, and β4 nAChR subunits, revealing its broader pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at α4β2 and α3β2-nAChRs (IC50 ~0.17 and >3 μM, respectively) expressed in Xenopus oocytes. In contrast, at α7-nAChRs, SLURP-2 significantly enhances acetylcholine-evoked currents at concentrations <1 μM but induces inhibition at higher concentrations. SLURP-2 allosterically interacts with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of human oral keratinocytes via interactions with α3β2-nAChRs, while it inhibited cell growth via α7-nAChRs. SLURP-2/mAChRs interactions are also probably involved in the control of keratinocyte growth. Computer modeling revealed possible SLURP-2 binding to the ‘classical’ orthosteric agonist/antagonist binding sites at α7 and α3β2-nAChRs.

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mentioning

confidence: 99%

Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors

Lyukmanova

Shulepko

Шенкарев

et al. 2016

Sci Rep

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“…The nAChR‐mediated transduction pathway can regulate keratinocyte function. Also, many immune cells including T cells, B cells leukemic cell lines and thymocyte, have active nAChR and nicotine binding to these receptors interferes with immune cell signaling . What is more, it is believed that smoking is positively related to an increased risk of psoriatic comorbidity including cardiovascular diseases…”

Section: Mechanisms Of Environmental Risk Factors’ Impact On Psoriasismentioning

confidence: 99%

Critical role of environmental factors in the pathogenesis of psoriasis

Zeng

Luo

Huang

et al. 2017

The Journal of Dermatology

177

142

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Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors.

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“…LYNX1 also inhibits SRC activation, suppressing mucin expression in the airway epithelium [ 69 ]. The LYNX1 gene is positioned in close proximity to SLURP2 , leading to the mistaken idea that they are alternatively spliced isoforms of the same gene, a theory which was disproved recently [ 70 ]. LYNX1 is one of the genes that has shown accelerated evolution in humans relative to other primates, correlating with the increased brain size and complexity [ 71 ].…”

Section: Ly6/neurotoxin-1mentioning

confidence: 99%

“…SLURP2 is expressed by human epidermal and oral keratinocytes, from where it is secreted into sweat and saliva, respectively [ 100 ]. SLURP2 expression is strongly induced in psoriatic skin lesions possibly by IL22, and is blocked by IFNG [ 70 , 101 ]. SLURP2 blocks the effect of acetylcholine by binding CHRNA3 (α3nAChR), and delays keratinocyte differentiation and prevents apoptosis [ 100 ].…”

Section: Secreted Ly6/urokinase-type Plasminogen Activator Receptor-rmentioning

confidence: 99%

“…SLURP2 blocks the effect of acetylcholine by binding CHRNA3 (α3nAChR), and delays keratinocyte differentiation and prevents apoptosis [ 100 ]. Although the SLURP2 and LYNX1 genes are closely linked leading to a mistaken idea that they are isoforms, it is now clear that they constitute separate transcription units that are differently regulated [ 70 ]. Slurp2−/− mice also develop signs of palmoplantar keratoderma and neuromuscular abnormality (hind-limb clasping) reminiscent of those seen in Slurp1−/− mice [ 99 , 102 ].…”

Section: Secreted Ly6/urokinase-type Plasminogen Activator Receptor-rmentioning

confidence: 99%

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Organization, evolution and functions of the human and mouse Ly6/uPAR family genes

et al. 2016

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Members of the lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily of proteins are cysteine-rich proteins characterized by a distinct disulfide bridge pattern that creates the three-finger Ly6/uPAR (LU) domain. Although the Ly6/uPAR family proteins share a common structure, their expression patterns and functions vary. To date, 35 human and 61 mouse Ly6/uPAR family members have been identified. Based on their subcellular localization, these proteins are further classified as GPI-anchored on the cell membrane, or secreted. The genes encoding Ly6/uPAR family proteins are conserved across different species and are clustered in syntenic regions on human chromosomes 8, 19, 6 and 11, and mouse Chromosomes 15, 7, 17, and 9, respectively. Here, we review the human and mouse Ly6/uPAR family gene and protein structure and genomic organization, expression, functions, and evolution, and introduce new names for novel family members.

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Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: A special reference to the nested gene LYNX1

Cited by 15 publications

References 17 publications

Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors

Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors

Critical role of environmental factors in the pathogenesis of psoriasis

Organization, evolution and functions of the human and mouse Ly6/uPAR family genes

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