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PH20在小鼠中枢神经系统和少突胶质前体细胞中不表达。

PH20 is not expressed in murine CNS and oligodendrocyte precursor cells.

作者信息

Marella Mathieu, Ouyang Joe, Zombeck Jonathan, Zhao Chunmei, Huang Lei, Connor Robert J, Phan Kim B, Jorge Michael C, Printz Marie A, Paladini Rudolph D, Gelb Arnold B, Huang Zhongdong, Frost Gregory I, Sugarman Barry J, Steinman Lawrence, Wei Ge, Shepard H Michael, Maneval Daniel C, Lapinskas Paula J

机构信息

Halozyme Therapeutics, Inc. San Diego California.

Biomodels LLC Watertown Massachusetts.

出版信息

Ann Clin Transl Neurol. 2017 Feb 23;4(3):191-211. doi: 10.1002/acn3.393. eCollection 2017 Mar.

DOI:10.1002/acn3.393
PMID:28275653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5338182/
Abstract

OBJECTIVE

Expression of /PH20 and its modulation of high/low molecular weight hyaluronan substrate have been proposed to play an important role in murine oligodendrocyte precursor cell (OPC) maturation in vitro and in normal and demyelinated central nervous system (CNS). We reexamined this using highly purified PH20.

METHODS

Steady-state expression of mRNA in OPCs was evaluated by quantitative polymerase chain reaction; the role of PH20 in bovine testicular hyaluronidase (BTH) inhibition of OPC differentiation was explored by comparing BTH to a purified recombinant human PH20 (rHuPH20). Contaminants in commercial BTH were identified and their impact on OPC differentiation characterized. /PH20 expression in normal and demyelinated mouse CNS tissue was investigated using deep RNA sequencing and immunohistological methods with two antibodies directed against recombinant murine PH20.

RESULTS

BTH, but not rHuPH20, inhibited OPC differentiation in vitro. Basic fibroblast growth factor (bFGF) was identified as a significant contaminant in BTH, and bFGF immunodepletion reversed the inhibitory effects of BTH on OPC differentiation. mRNA was undetected in OPCs in vitro and in vivo; PH20 immunolabeling was undetected in normal and demyelinated CNS.

INTERPRETATION

We were unable to detect /PH20 expression in OPCs or in normal or demyelinated CNS using the most sensitive methods currently available. Further, "BTH" effects on OPC differentiation are not due to PH20, but may be attributable to contaminating bFGF. Our data suggest that caution be exercised when using some commercially available hyaluronidases, and reports of /PH20 morphogenic activity in the CNS may be due to contaminants in reagents.

摘要

目的

有人提出，/PH20的表达及其对高/低分子量透明质酸底物的调节作用，在体外培养的小鼠少突胶质前体细胞（OPC）成熟过程中，以及在正常和脱髓鞘的中枢神经系统（CNS）中发挥重要作用。我们使用高度纯化的PH20对此进行了重新研究。

方法

通过定量聚合酶链反应评估OPC中mRNA的稳态表达；通过将牛睾丸透明质酸酶（BTH）与纯化的重组人PH20（rHuPH20）进行比较，探讨PH20在BTH抑制OPC分化中的作用。鉴定了商业BTH中的污染物，并表征了它们对OPC分化的影响。使用深度RNA测序和免疫组织学方法，用两种针对重组鼠PH20的抗体，研究正常和脱髓鞘小鼠CNS组织中的/PH20表达。

结果

BTH而非rHuPH20在体外抑制OPC分化。碱性成纤维细胞生长因子（bFGF）被鉴定为BTH中的一种重要污染物，bFGF免疫去除可逆转BTH对OPC分化的抑制作用。在体外和体内的OPC中均未检测到mRNA；在正常和脱髓鞘的CNS中未检测到PH20免疫标记。

解读

我们无法使用目前最敏感的方法在OPC或正常或脱髓鞘的CNS中检测到/PH20表达。此外，“BTH”对OPC分化的影响并非由于PH20，而可能归因于污染的bFGF。我们的数据表明，在使用某些市售透明质酸酶时应谨慎，并且CNS中/PH20形态发生活性的报道可能归因于试剂中的污染物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/ce8c6760c55a/ACN3-4-191-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/264d1d97132a/ACN3-4-191-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/240de6d7d125/ACN3-4-191-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/9282f7a20e5b/ACN3-4-191-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/61a2403bcd2b/ACN3-4-191-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/6004ef0680a1/ACN3-4-191-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/8a0718f8c9bb/ACN3-4-191-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/240de6d7d125/ACN3-4-191-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/9282f7a20e5b/ACN3-4-191-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/61a2403bcd2b/ACN3-4-191-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/c15b40ab5087/ACN3-4-191-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3201/5338182/ce8c6760c55a/ACN3-4-191-g010.jpg

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