SuperGAG biopolymers for treatment of excessive bladder permeability.
SuperGAG biopolymers for treatment of excessive bladder permeability.
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SuperGAG生物聚合物用于治疗过度膀胱渗透性。
DOI：
10.1002/prp2.709
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发表时间：
2021-03
影响因子：
2.6
通讯作者：
Hurst RE
中科院分区：
文献类型：
--
作者：
Towner RA;Greenwood-Van Meerveld B;Mohammadi E;Saunders D;Smith N;Sant GR;Shain HC;Jozefiak TH;Hurst RE
治疗IC/BPS的治疗方案很少。利用CS的可控寡聚反应合成了一种新型的高分子量GAG生物聚合物（SuperGAG），经TFF纯化，并用SEC - mall和1H - NMR对其进行了表征。改良的GAG生物聚合物在OVX雌性大鼠模型中进行了测试，该模型通过用稀释的（1mg /ml）硫酸鱼精蛋白在囊内治疗10分钟诱导膀胱渗透性，并在用SuperGAG、硫酸软骨素或生理盐水治疗后用经典的Ussing Chamber TEER测量测量。采用von Frey纤维法评价其对消除腹痛反应的效果。SuperGAG生物聚合物随后在第二种转基因小鼠模型（URO - MCP1）中进行了研究，该模型越来越被认为是IC/BPS的模型。通过短暂暴露于亚毒性剂量的LPS诱导渗透性，并使用对比增强MRI （CE - MRI）进行量化。SuperGAG生物聚合物将OVX大鼠模型的不渗透性恢复到正常水平，通过Ussing室的TEER测量，并减少了由诱导渗透性引起的腹痛反应。URO - MCP1小鼠模型的评估也显示了膀胱不渗透性的恢复，并显示了CE - MRI成像在评估药物恢复膀胱不渗透性的功效方面的实用性。我们得出结论，新型高分子量SuperGAG生物聚合物可以有效地恢复尿路上皮的不渗透性，减少尿路上皮上GAG层缺失所产生的疼痛。SuperGAG生物聚合物可以为IC/BPS提供一种新颖有效的新治疗方法，特别是如果与MRI相结合来评估治疗效果。类似蛋白多糖的“SuperGAG”可恢复膀胱的不渗透性并消除腹痛。supergag有望成为治疗间质性膀胱炎/膀胱疼痛综合征（IC/BPS）的新疗法。
Few therapeutic options exist for treatment of IC/BPS. A novel high MW GAG biopolymer (“SuperGAG”) was synthesized by controlled oligomerization of CS, purified by TFF and characterized by SEC‐MALLS and 1H‐NMR spectroscopy. The modified GAG biopolymer was tested in an OVX female rat model in which bladder permeability was induced by a 10‐minute intravesicular treatment with dilute (1 mg/ml) protamine sulfate and measured by classical Ussing Chamber TEER measurements following treatment with SuperGAG, chondroitin sulfate, or saline. The effect on abrogating the abdominal pain response was assessed using von Frey filaments. The SuperGAG biopolymer was then investigated in a second, genetically modified mouse model (URO‐MCP1) that increasingly is accepted as a model for IC/BPS. Permeability was induced with a brief exposure to a sub‐noxious dose of LPS and was quantified using contrast‐enhanced MRI (CE‐MRI). The SuperGAG biopolymer restored impermeability to normal levels in the OVX rat model as measured by TEER in the Ussing chamber and reduced the abdominal pain response arising from induced permeability. Evaluation in the URO‐MCP1 mouse model also showed restoration of bladder impermeability and showed the utility of CE‐MRI imaging for evaluating the efficacy of agents to restore bladder impermeability. We conclude novel high MW SuperGAG biopolymers are effective in restoring urothelial impermeability and reducing pain produced by loss of the GAG layer on the urothelium. SuperGAG biopolymers could offer a novel and effective new therapy for IC/BPS, particularly if combined with MRI to assess the efficacy of the therapy. Proteoglycan‐like “SuperGAG” restores bladder impermeability and abrogates abdominal pain. SuperGAGs could serve as novel therapies for interstitial cystitis/ bladder pain syndrome (IC/BPS).
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影响因子：
2.7
作者：
Fitzgerald, Jocelyn J.;Ustinova, Elena;Koronowski, Kevin B.;de Groat, William C.;Pezzone, Michael A.
通讯作者：
Pezzone, Michael A.
影响因子：
6.6
作者：
Nickel, J. Curtis;Tripp, Dean A.;Nordling, Jorgen
通讯作者：
Nordling, Jorgen
DOI：
10.1152/ajprenal.00566.2015
发表时间：
2016-05-15
影响因子：
4.2
作者：
Hurst, Robert E.;Van Gordon, Samuel;Greenwood-Van Meerveld, Beverley
通讯作者：
Greenwood-Van Meerveld, Beverley
影响因子：
23.4
作者：
Humphrey, Louise;Arbuckle, Rob;Abraham, Lucy
通讯作者：
Abraham, Lucy
影响因子：
6.6
作者：
Parsons, C. Lowell;Proctor, Jeffrey;Argade, Sulabha
通讯作者：
Argade, Sulabha