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Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination.
ASN Neuro ( IF 4.7 ) Pub Date : 2017-12-05 , DOI: 10.1177/1759091417745425 Jihyun Kim 1 , Anthony Elias 1 , Taeweon Lee 2 , Patrice Maurel 1 , Haesun A Kim 1
ASN Neuro ( IF 4.7 ) Pub Date : 2017-12-05 , DOI: 10.1177/1759091417745425 Jihyun Kim 1 , Anthony Elias 1 , Taeweon Lee 2 , Patrice Maurel 1 , Haesun A Kim 1
Affiliation
Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of various metalloproteinases including matrix metalloproteinases and ADAM family proteins. In the peripheral nervous system, ADAM17, also known as TNF-α converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type III, an axonal growth factor that is essential for Schwann cell myelination. The processing by ADAM17 attenuates Nrg1 signaling and inhibits Schwann cell myelination. TIMP-3 targets ADAM17, suggesting a possibility that TIMP-3 may elicit a promyelinating function in Schwann cells by relieving ADAM17-induced myelination block. To investigate this, we used a myelinating coculture system to determine the effect of TIMP-3 on Schwann cell myelination. Treatment with TIMP-3 enhanced myelin formation in cocultures, evident by an increase in the number of myelin segments and upregulated expression of Krox20 and myelin protein. The effect of TIMP-3 was accompanied by the inhibition of ADAM17 activity and an increase in Nrg1 type III signaling in cocultures. Accordingly, the N-terminus fragment of TIMP-3, which exhibits a selective inhibitory function toward ADAM17, elicited a similar myelination-promoting effect and increased Nrg1 type III activity. TIMP-3 also enhanced laminin production in cocultures, which is likely to aid Schwann cell myelination.
中文翻译:
金属蛋白酶3的组织抑制剂可促进雪旺氏细胞的髓鞘形成。
金属蛋白酶3(TIMP-3)的组织抑制剂可抑制各种金属蛋白酶的活性,包括基质金属蛋白酶和ADAM家族蛋白。在周围神经系统中,ADAM17,也称为TNF-α转换酶(TACE),可切割Nrg1型III的胞外域,轴突生长因子对Schwann细胞的髓鞘形成至关重要。ADAM17的处理减弱了Nrg1信号传导并抑制了雪旺氏细胞的髓鞘形成。TIMP-3靶向ADAM17,提示TIMP-3可能通过减轻ADAM17诱导的髓鞘形成阻滞而在雪旺细胞中引起早髓鞘功能。为了对此进行研究,我们使用了有髓鞘的共培养系统来确定TIMP-3对雪旺细胞髓鞘形成的影响。TIMP-3处理可增强共培养物中的髓磷脂形成,髓磷脂节段数量的增加和Krox20和髓磷脂蛋白表达的上调明显证明了这一点。在共培养中,TIMP-3的作用伴随着ADAM17活性的抑制和Nrg1 III型信号传导的增加。因此,TIMP-3的N末端片段表现出对ADAM17的选择性抑制功能,引发了类似的髓鞘促进作用并增加了Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。引起类似的髓鞘促进作用并增加Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。引起类似的髓鞘促进作用并增加Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。
更新日期:2019-11-01
中文翻译:
金属蛋白酶3的组织抑制剂可促进雪旺氏细胞的髓鞘形成。
金属蛋白酶3(TIMP-3)的组织抑制剂可抑制各种金属蛋白酶的活性,包括基质金属蛋白酶和ADAM家族蛋白。在周围神经系统中,ADAM17,也称为TNF-α转换酶(TACE),可切割Nrg1型III的胞外域,轴突生长因子对Schwann细胞的髓鞘形成至关重要。ADAM17的处理减弱了Nrg1信号传导并抑制了雪旺氏细胞的髓鞘形成。TIMP-3靶向ADAM17,提示TIMP-3可能通过减轻ADAM17诱导的髓鞘形成阻滞而在雪旺细胞中引起早髓鞘功能。为了对此进行研究,我们使用了有髓鞘的共培养系统来确定TIMP-3对雪旺细胞髓鞘形成的影响。TIMP-3处理可增强共培养物中的髓磷脂形成,髓磷脂节段数量的增加和Krox20和髓磷脂蛋白表达的上调明显证明了这一点。在共培养中,TIMP-3的作用伴随着ADAM17活性的抑制和Nrg1 III型信号传导的增加。因此,TIMP-3的N末端片段表现出对ADAM17的选择性抑制功能,引发了类似的髓鞘促进作用并增加了Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。引起类似的髓鞘促进作用并增加Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。引起类似的髓鞘促进作用并增加Nrg1 III型活性。TIMP-3还增强了共培养物中层粘连蛋白的产生,这可能有助于雪旺细胞的髓鞘形成。