Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.
Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.
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普罗蛋白转化酶枯草蛋白/KEXIN 9型是牛皮癣敏感性基因座，与IL36G负相关。
DOI：
10.1172/jci.insight.141193
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发表时间：
2022-08-22
期刊：
影响因子：
8
通讯作者：
Maverakis, Emanual
中科院分区：
文献类型：
--
作者：
Merleev, Alexander;Ji-Xu, Antonio;Toussi, Atrin;Tsoi, Lam C.;Le, Stephanie T.;Luxardi, Guillaume;Xing, Xianying;Wasikowski, Rachael;Liakos, William;Brueggen, Marie-Charlotte;Elder, James T.;Adamopoulos, Iannis E.;Izumiya, Yoshihiro;Leal, Annie R.;Li, Qinyuan;Kuzminykh, Nikolay Y.;Kirane, Amanda;Marusina, Alina, I;Gudjonsson, Johann E.;Maverakis, Emanual
枯草杆菌蛋白原转换酶9(PCSK9)是低密度脂蛋白受体(LDLR)的翻译后调节因子。最近的研究提出了PCSK9在调节免疫反应中的作用。通过基于RNA-Seq的变异发现，我们确定了位于PCSK9(rs662145 C>；T)内的1p32.3处可能的银屑病易感基因。这一发现在独立获得的基因组和RNA-Seq数据集中得到了验证。单细胞RNA-Seq(scRNA-Seq)鉴定角质形成细胞是人类皮肤中PCSK9的主要来源。然而，PCSK9在角质形成细胞亚群中的表达并不一致。ScRNA-Seq和IHC显示PCSK9的表皮梯度，在基底层和早期棘层角质形成细胞中表达最高，在颗粒层角质形成细胞中表达最低。IL36G的表达与之相反，在颗粒层角质形成细胞中表达最强。PCSK9 siRNA敲除实验证实了PCSK9和IL36G表达之间的这种反向关系。其他免疫基因也与PCSK9的表达有关，包括IL27RA、IL1RL1、ISG20和STX3。在培养的角质形成细胞和正常人皮肤中，与杂合皮肤或细胞系相比，PCSK9 SNP rs662145 C>；T纯合与PCSK9低表达和IL36G高表达相关。总之，这些结果支持PCSK9是银屑病的易感基因，并在PCSK9和炎性细胞因子的表达之间建立了假定的联系。
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed a role for PCSK9 in regulating immune responses. Using RNA-Seq–based variant discovery, we identified a possible psoriasis-susceptibility locus at 1p32.3, located within PCSK9 (rs662145 C > T). This finding was verified in independently acquired genomic and RNA-Seq data sets. Single-cell RNA-Seq (scRNA-Seq) identified keratinocytes as the primary source of PCSK9 in human skin. PCSK9 expression, however, was not uniform across keratinocyte subpopulations. scRNA-Seq and IHC demonstrated an epidermal gradient of PCSK9, with expression being highest in basal and early spinous layer keratinocytes and lowest in granular layer keratinocytes. IL36G expression followed the opposite pattern, with expression highest in granular layer keratinocytes. PCSK9 siRNA knockdown experiments confirmed this inverse relationship between PCSK9 and IL36G expression. Other immune genes were also linked to PCSK9 expression, including IL27RA, IL1RL1, ISG20, and STX3. In both cultured keratinocytes and nonlesional human skin, homozygosity for PCSK9 SNP rs662145 C > T was associated with lower PCSK9 expression and higher IL36G expression, when compared with heterozygous skin or cell lines. Together, these results support PCSK9 as a psoriasis-susceptibility locus and establish a putative link between PCSK9 and inflammatory cytokine expression.
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DOI：
10.1016/j.jid.2018.07.046
发表时间：
2019-04
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Luan C;Chen X;Zhu Y;Osland JM;Gerber SD;Dodds M;Hu Y;Chen M;Yuan R
通讯作者：
Yuan R
影响因子：
15.9
作者：
Dillen, Carly A.;Pinsker, Bret L.;Miller, Lloyd S.
通讯作者：
Miller, Lloyd S.
影响因子：
6.5
作者：
Li, Bingshan;Tsoi, Lam C.;Swindell, William R.;Gudjonsson, Johann E.;Tejasvi, Trilokraj;Johnston, Andrew;Ding, Jun;Stuart, Philip E.;Xing, Xianying;Kochkodan, James J.;Voorhees, John J.;Kang, Hyun M.;Nair, Rajan P.;Abecasis, Goncalo R.;Elder, James T.
通讯作者：
Elder, James T.
影响因子：
7
作者：
McKenna, Aaron;Hanna, Matthew;DePristo, Mark A.
通讯作者：
DePristo, Mark A.
DOI：
10.1016/j.jid.2020.05.115
发表时间：
2021-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Garshick MS;Baumer Y;Dey AK;Grattan R;Ng Q;Teague HL;Yu ZX;Chen MY;Tawil M;Barrett TJ;Underberg J;Fisher EA;Krueger J;Powell-Wiley TM;Playford MP;Berger JS;Mehta NN
通讯作者：
Mehta NN