SHH 蛋白, Human

Sonic Hedgehog (SHH) Protein is a secretory glycoprotein of the Hedgehog family that can self-cleave to form N-SHH. SHH Protein activates Smo by binding to Frizzled and LRP6, inhibits GSK-3β to stabilize β-catenin, and activates FOXM1. SHH Protein also promotes NO release and shortens myocardial APD by phosphorylating eNOS through PI3K/Akt. SHH Protein can promote the maturation of sweat gland cells in three-dimensional culture and play a cardioprotective role in the pig ischemia-reperfusion model^[1][2]. SHH Protein, Human is a recombinant human SHH protein expressed in E. coli with tag-free.

Sonic Hedgehog (SHH) Protein 是 Hedgehog 家族的分泌型糖蛋白，其转录受到包含多个增强子的长程调控机制的调节。SHH Protein 的 N 端含半胱氨酸富集域与糖基化位点，C 端具胆固醇结合域，可通过自剪切形成 N 端活性片段 (N-SHH)。在内质网中，ShhC 被降解，留下对发育模式至关重要的脂化 ShhNp。SHH Protein 通过切割和翻译后修饰进行了大量修饰，并且其从生产细胞中的释放也可以通过与 Dispatched、Scube2 和硫酸乙酰肝素蛋白聚糖的相互作用来调节。
SHH 信号参与胚胎发育 (包括肺) 以及发育过程中的模式形成。SHH Protein 作为经典Hedgehog 信号通路配体，其与跨膜受体 Frizzled (如 Frizzled-1) 及共受体 LRP6 结合，激活 Smoothened (Smo) 并抑制 GSK-3β，解除 β-catenin 降解使其核转位，激活 FOXM1 等抗凋亡基因。同时，SHH Protein 可通过 PI3K/Akt 通路磷酸化 eNOS 促进 NO 释放，缩短心肌细胞动作电位时程 (APD)。SHH Protein 的生物学活性包括促进三维培养中汗腺细胞成熟 (上调 CK19 等标志物) 及猪缺血再灌注模型中心肌保护 (减少梗死体积、抑制心律失常)，主要用于组织工程 (汗腺再生)、缺血性疾病 (如心肌梗死)、前列腺癌等疾病的研究^{[1][2][3][4][5]}。

SHH Protein (人源；40 ng/mL；21 天) 可激活三维培养的人汗腺细胞中 Shh 信号通路 (上调 Smo、Gli-1/2 表达)，促进汗腺管状结构形成，并显著上调分泌区标志物 CK19、CEA、EDA 及 EDAR 的 mRNA 和蛋白表达水平^[3]。

SHH Protein (人源；25 μg/kg；冠状动脉闭塞后 15 分钟，静脉注射；单剂量) 在不同时间的猪短暂性冠状动脉闭塞的再灌注模型 (25 分钟、40 分钟) 中，显著降低室颤发生率及心律失常评分；在 40 分钟模型中，降低血清心肌损伤标志物 cTnI 和 FABP 水平，伴随 eNOS 磷酸化激活^[4]。
SHH Protein (人源；625 μg/kg MPs^SHH+；冠状动脉闭塞后 15 分钟，静脉注射；单剂量) 在 40 分钟的猪持续性冠状动脉闭塞再灌注模型中，减少梗死面积，显著降低血清 cTnI 和 FABP 水平^[4]。

Measured by its ability to induce alkaline phosphatase production by C3H10T1/2 mouse embryonic fibroblast cells. The ED₅₀ for this effect is ≤ 0.3049 µg/mL, corresponding to a specific activity is ≥3.279×10³ units/mg.

• 
  Measured by its ability to induce alkaline phosphatase production by C3H10T1/2 mouse embryonic fibroblast cells. The ED₅₀ for this effect is 0.07853 µg/mL, corresponding to a specific activity is 1.27×10⁴ units/mg.

Human

E. coli

Tag Free

Q15465 (C24-G197)

6469  [NCBI]

Partial

CGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGG

Approximately 20 kDa

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

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of 20 mM PB, 100 mM NaCl, 1 mM DTT, pH 7.5 or PBS, pH 7.4, 5% trehalose, 5% mannitol and 0.01% Tween80 or PBS, pH 7.4, 8% trehalose.

<1 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]. Wang XZ, et al. Sonic hedgehog (Shh) and CC chemokine ligand 2 signaling pathways in asthma. J Chin Med Assoc. 2019;82(5):343-350.  [Content Brief]

  [2]. Seo H, et al. Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning. J Dent Res. 2018;97(9):1055-1063.  [Content Brief]

  [3]. Huang Z, et al. Shh promotes sweat gland cell maturation in three-dimensional culture. Cell Tissue Bank. 2016 Jun;17(2):317-25.  [Content Brief]

  [4]. Ghaleh B, et al. Cardioprotective effect of sonic hedgehog ligand in pig models of ischemia reperfusion. Theranostics. 2020 Mar 4;10(9):4006-4016.  [Content Brief]

  [5]. Spinella-Jaegle S, et al. Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci. 2001 Jun;114(Pt 11):2085-94.  [Content Brief]