MMP-mediated cleavage of beta-dystroglycan in myelin sheath is involved in autoimmune neuritis.
Alpha-/beta-dystroglycans (DG) located at the outmost layer of myelin sheath play a critical role in its formation and stability in the peripheral nerve system. The demyelination of nerve fibers is present in autoimmune neuritis, however, it is not known about the molecular mechanisms underlying this pathological process. In an animal model of experimental autoimmune neuritis, we observed that beta-DG cleavage was associated with the demyelination of peripheral nerves. The neuritis and beta-DG cleavage were accompanied by matrix metalloproteinase (MMP)-2/-9 over-expressions and attenuated by captopril, a MMP inhibitor. The blockade of MMPs also improves clinical signs. Our results reveal a crucial role of MMP-mediated beta-DG cleavage in autoimmune neuritis, such as Guillain-Barre' syndrome, and bring insights into therapeutic strategies for autoimmune diseases.
Zhao
Xiu Li
XL
Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Li
Guo Zhong
GZ
Sun
Bo
B
Zhang
Zhong Ling
ZL
Yin
Yan Hong
YH
Tian
Yu Shuang
YS
Li
He
H
Li
Hu Lun
HL
Wang
De Sheng
de S
Zhong
Di
D
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D020275:Guillain-Barre Syndrome / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D049030:Dystroglycans; D002216:Captopril; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9