RSPO1/R-spondin-1 蛋白, Human (CHO, His)

RSPO1/R-spondin-1 is a potent activator of the Wnt/β-catenin signaling pathway and a secretory glycoprotein belonging to the R-spondin family. RSPO1 homotetramers synergize with LRP5/6 via LGR4/5/6 and activate the Wnt/β-catenin pathway by inhibiting DKK1/Kremen-mediated LRP6 endocytosis. RSPO1 promotes β-catenin nuclear translocation, drives HSC activation in liver fibrosis, inhibits adipocyte thermogenic gene expression, and promotes intestinal epithelial proliferation^[1][2][3][4]. RSPO1/R-spondin-1 Protein, Human (CHO, His) is a recombinant human RSPO1 protein expressed in CHO cells with a C-6*His tag.

1. RSPO1/R-spondin-1 的蛋白特点
RSPO1/R-spondin-1，属于 R-Spondin (RSpo) 分泌蛋白家族 (含 RSPO1-4 成员)，是 Wnt/-catenin 信号通路的有效激活剂^[1]。RSPO1/R-spondin-1 是由二硫键连接的分泌型糖蛋白，含 N 端信号肽、两个 furin 样结构域 (FR)、血栓 ospondin 1 结构域 (TSP1) 及 C 端带正电荷区域，通过静电作用结合肝素硫酸盐蛋白聚糖 (HSPG) 锚定细胞外基质^[1][3]。
R-spondin-1/RSPO1 活性很大程度上取决于经典 Wnt 配体和 LRP6 的存在。虽然 R-spondin-1/RSPO1 不会直接激活 LRP6，但可以干扰 DKK1 功能，调节 LRP5 或 LRP6 受体的周转并放大 Wnt 依赖性信号传导^[2]。RSPO1/R-spondin-1 通过抑制 DKK1/Kremen 介导的 LRP6 内吞，维持细胞表面 LRP6 水平，激活 Wnt/β-catenin 通路。与 LGR4/5/6 结合后，解除 ZNRF3/RNF43 对 Wnt 受体的泛素化降解，促进 β-catenin 核转位及 TCF/LEF 依赖的基因转录^[1][3]。

2. RSPO1/R-spondin-1 的应用
RSPO1/R-spondin-1 参与肝纤维化调控：RSPO1/R-spondin-1 可促进肝星状细胞 (HSC) 活化，上调 α-SMA 和 Collagen-I，通过 Wnt 通路驱动纤维化^[4]。
RSPO1/R-spondin-1 抑制脂肪代谢：野生型 RSPO1 通过 LGR4 增强 Wnt 信号，抑制脂肪细胞线粒体呼吸及产热基因 (UCP1、PGC-1α) 表达，而 p.R219W 突变因破坏 HSPG 结合，异常释放后加剧肥胖^[3]。
RSPO1/R-spondin-1 促进肠上皮增殖：RSPO1 通过 Wnt 通路促进肠隐窝干细胞增殖，修复黏膜损伤^[2]。

RSPO1/R-spondin-1 (人源；200 ng/mL；18 h) 在 HEK293 细胞中通过抑制 LRP6 内吞增强 Wnt 信号，促进 β-catenin 核转位及 TCF 报告基因活性^[1]。
RSPO1/R-spondin-1 (人源；100 ng/mL；24 h) 在小鼠脂肪前体细胞中抑制线粒体呼吸与产热基因表达，减少脂滴数量并激活 Wnt/β-catenin 通路^[3]。
RSPO1/R-spondin-1 Protein (人源；100 ng/mL；24 h) 在人肝星状细胞 (HSC) 中激活 Wnt/β-catenin 通路，上调 α-平滑肌肌动蛋白 (α-SMA) 和胶原蛋白 I 表达，促进细胞增殖并减少脂滴积累^[4]。

RSPO1/R-spondin-1 (人源；0.8 mg/kg；i.p.；每日 1 次；连续 80 天) 显著降低 Streptozotocin (HY-13753) 诱导小鼠糖尿病模型的血糖，改善葡萄糖耐受，促进 β 细胞功能和增殖^[5]。
RSPO1/R-spondin-1 (人源；0.4 mg/kg 或 0.8 mg/kg；i.p.；每日 1 次；18 周) 在非肥胖糖尿病 (NOD) 小鼠中延缓糖尿病进展，增加 β 细胞质量，维持正常血糖^[5]。
RSPO1/R-spondin-1 (人源；0.4 mg/kg 或 0.8 mg/kg；i.p.；每日 1 次；60 天) 在移植人类胰岛的 RAG12N2 免疫缺陷小鼠中，增加人类 β 细胞体积，增强 c-肽分泌功能^[5]。
RSPO1/R-spondin-1 (人源；2.4 mg/kg；i.p.；每周 1 次；18 周) 在 NOD 小鼠中通过 FC-RSPO1 优化类似物维持血糖正常，增加 β 细胞质量^[5]。<

1.R-Spondin-1 enhances BMP-2-mediated differentiation of MC3T3-E1 cells. The expected ED₅₀ is 1.182 μg/mL.corresponding to a specific activity is 8.46 ×10² units/mg.
2.Measured by its ability to induce Topflash reporter activity in HEK293T human embryonic kidney cells. The ED₅₀ for this effect is 1-10 ng/mL.

• 
  R-Spondin-1 enhances BMP-2-mediated differentiation of MC3T3-E1 cells. The expected ED₅₀ is 1.182 μg/ml.corresponding to a specific activity is  8.46 ×10^2 units/mg.

Human

CHO

C-6*His

Q2MKA7-1 (S21-A263)

284654  [NCBI]

Full Length of Isoform-1 Mature Protein

SRGIKGKRQRRISAEGSQACAKGCELCSEVNGCLKCSPKLFILLERNDIRQVGVCLPSCPPGYFDARNPDMNKCIKCKIEHCEACFSHNFCTKCKEGLYLHKGRCYPACPEGSSAANGTMECSSPAQCEMSEWSPWGPCSKKQQLCGFRRGSEERTRRVLHAPVGDHAACSDTKETRRCTVRRVPCPEGQKRRKGGQGRRENANRNLARKESKEAGAGSRRRKGQQQQQQQGTVGPLTSAGPA

Approximately 38-43.3 kDa, based on SDS-PAGE under reducing conditions.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末

Lyophilized after extensive dialysis against PBS, pH 7.4 or PBS,4%Mannitol,pH 7.4.

<0.01 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Binnerts ME, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14700-5.  [Content Brief]

  [2]. Zhao J, et al. Tipping the balance: modulating the Wnt pathway for tissue repair. Trends Biotechnol. 2009 Mar;27(3):131-6.  [Content Brief]

  [3]. Sun Y, et al. Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity. Adv Sci (Weinh). 2023 Apr;10(12):e2207152.  [Content Brief]

  [4]. Yin X, et al. RSPOs facilitated HSC activation and promoted hepatic fibrogenesis. Oncotarget. 2016 Sep 27;7(39):63767-63778.  [Content Brief]

  [5]. Silvano S, et al. RSPO1, a potent inducer of pancreatic β cell neogenesis. Cell Rep Med. 2025 May 20;6(5):102126.  [Content Brief]