明星指標：高(gao)表(biao)達(da)vimentin的(de)巨(ju)噬細(xi)胞在(zai)肝(gan)細胞癌(ai)免(mian)疫抑制(zhi)中的(de)關(guan)鍵作用(yong)

Vimentin (波形蛋白(bai)) 是(shi)壹種(zhong)在(zai)間(jian)充(chong)質(zhi)細(xi)胞中廣(guang)泛(fan)表(biao)達(da)的(de) III 型(xing)中間(jian)絲 (intermediate filament, IF) 蛋(dan)白(bai)。它(ta)在(zai)細(xi)胞骨(gu)架(jia)的(de)形(xing)成(cheng)、細(xi)胞的(de)形(xing)狀維(wei)持(chi)、細(xi)胞的(de)遷移(yi)、細(xi)胞信號(hao)傳(chuan)導以及(ji)細(xi)胞應激(ji)反(fan)應中發揮著重要(yao)作用(yong)。它(ta)通(tong)過側向或(huo)末(mo)端(duan)方(fang)式附著於細(xi)胞核(he)、內質(zhi)網和線(xian)粒(li)體，參與(yu)調(tiao)控(kong)細(xi)胞定向運動、取(qu)向排(pai)列(lie)、細(xi)胞片層組織形成(cheng)，並在(zai)細(xi)胞遷移(yi)前(qian)沿(yan)維(wei)持(chi)高(gao)爾基(ji)體極(ji)性(xing)。此(ci)外(wai)，波(bo)形蛋白(bai)通(tong)過細胞接觸(chu)依賴機(ji)制(zhi)保護(hu)SCRIB蛋白(bai)免(mian)受(shou)蛋(dan)白(bai)酶體降(jiang)解，並促進(jin)其(qi)定位(wei)於中(zhong)間(jian)絲結(jie)構(gou)

Vimentin結(jie)構(gou). Schematic representation of a vimentin filament from a monomer to its assembly into a mature filament. The vimentin monomer is composed of a central a-helical domain flanked by an unstructured head and tail domain. On the central domain, vimentin possesses a rod II domain with lectin-like properties.

重要發現：Vimentin高表(biao)達(da)（VIM+）巨(ju)噬細(xi)胞通過(guo)分(fen)泌(mi)IL-1β激(ji)活(huo)Treg細(xi)胞的(de)免(mian)疫抑制(zhi)功(gong)能

復旦(dan)大學(xue)的(de)王紅(hong)陽/陳(chen)磊(lei)教授團(tuan)隊(dui)於(yu)2024年(nian)9月在(zai)Nature Cancer （IF：23.5）上(shang)發表(biao)了題(ti)為“Spatial single-cell protein landscape reveals vimentinhigh macrophages as immune-suppressive in the microenvironment of hepatocellular carcinoma"的(de)研(yan)究(jiu)性(xing)文(wen)章。該(gai)文繪(hui)制(zhi)了(le)HCC單(dan)細胞空間(jian)蛋(dan)白(bai)圖(tu)譜，解析了HCC腫(zhong)瘤間(jian)空(kong)間(jian)異質(zhi)性(xing)，建立了(le)預後(hou)相關(guan)的(de)幹(gan)細胞癌(ai)（HCC）空(kong)間(jian)分(fen)型(xing)（Spatial Pattern），並整合多組學(xue)和(he)體(ti)外(wai)實驗揭(jie)示(shi)了Vimentin高表(biao)達(da)的(de)巨(ju)噬細(xi)胞與(yu)Treg細(xi)胞的(de)空(kong)間(jian)互(hu)作(zuo)促(cu)進HCC的(de)疾病(bing)進(jin)展。

該項(xiang)研(yan)究(jiu)通過(guo)開展了單(dan)細胞測(ce)序和空間(jian)轉錄組(zu)分(fen)析(xi)，揭示(shi)了VIM+巨噬細(xi)胞的(de)基(ji)因(yin)表(biao)達(da)特(te)征(zheng)，發現了VIM+巨(ju)噬細(xi)胞和Treg之間(jian)基(ji)因(yin)表(biao)達(da)的(de)高(gao)度(du)關(guan)聯性(xing)，提(ti)示(shi)了VIM+巨噬細(xi)胞可能(neng)作(zuo)用於(yu)Treg，從而增(zeng)強(qiang)免(mian)疫抑制(zhi)。配受(shou)體(ti)分(fen)析(xi)進壹步(bu)揭(jie)示(shi)了VIM+巨噬細(xi)胞或許通(tong)過(guo)白(bai)介素-1β（IL-1β）和幹(gan)擾素-γ（IFN-γ）參與(yu)對(dui)Treg細胞的(de)調(tiao)控。隨(sui)後(hou)，作者利用(yong)流(liu)式細胞儀分(fen)離(li)了VIM+和VIM低表(biao)達(da)的(de)巨(ju)噬細(xi)胞，並檢測(ce)了其中(zhong)IL-1β的(de)表(biao)達(da)水(shui)平。結(jie)果(guo)表(biao)明，在(zai)不(bu)同類(lei)型(xing)的(de)巨(ju)噬細(xi)胞中，VIM+的(de)巨(ju)噬細(xi)胞顯著(zhu)高(gao)表(biao)達(da)IL-1β，細(xi)胞共(gong)培(pei)養實(shi)驗發現了VIM+巨(ju)噬細(xi)胞促進(jin)Treg分(fen)泌(mi)IL-10，而加入IL-1β抗體可顯(xian)著(zhu)緩解作用效(xiao)果(guo)。

斯(si)達(da)特(te)S-RMab® 

Vimentin Recombinant Rabbit mAb (SDT-029-120) （貨(huo)號(hao)：S0B2254）抗體是(shi)您Vimentin 研(yan)究(jiu)中的(de)有(you)力幫(bang)手(shou)。

數(shu)據(ju)驗證(zheng)：

WB免疫印(yin)記(ji)

WB result of Vimentin Rabbit mAb

Primary antibody: Vimentin Rabbit mAb at 1/500 dilution

Lane 1: Daudi whole cell lysate 20 µg

Lane 2: HeLa whole cell lysate 20 µg

Lane 3: A549 whole cell lysate 20 µg

Negative control: Daudi whole cell lysate

Secondary antibody: Goat Anti-Rabbit IgG, (H+L), HRP conjugated at 1/10000 dilution

Predicted MW: 54 kDa

Observed MW: 57 kDa

IHC 免疫組化(hua)

斯達(da)特(te)S-RMab® 系(xi)列(lie)抗體賦能(neng)生(sheng)命科(ke)學(xue)和(he)病(bing)理(li)研究(jiu)

免疫細胞化學(xue)

ICC shows positive staining in HeLa cells. Anti-Vimentin antibody was used at 1/250 dilution (Green) and incubated overnight at 4°C. Goat polyclonal Antibody to Rabbit IgG - H&L (Alexa Fluor® 488) was used as secondary antibody at 1/1000 dilution. The cells were fixed with 4% PFA and permeabilized with 0.1% PBS-Triton X-100. Nuclei were counterstained with DAPI (Blue).Counterstain with tubulin (Red).

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