Sains Malaysiana 50(11)(2021): 3313-3320

http://doi.org/10.17576/jsm-2021-5011-15

MiR-122-5p Attenuates Endothelial-to-Mesenchymal Transition Induced by Oxygen and Glucose Deprivation/Reperfusion

(MiR-122-5p Mengatenuasi Peralihan Endotelium-kepada-Mesenkim Teraruh oleh Kekurangan Oksigen dan Glukosa/Reperfusi)

HAIYAN YU¹, JINQIU XU², PENGYIN ZHU³ & CHUNYAN ZHANG²*

¹Intensive Care Unit, Shanghai Quyang Hospital, Shanghai, China

²Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China

³Department of Pharmacy, Affiliated Hai’an Peoples’ Hospital of Nantong University, Nantong, China

Diserahkan: 11 Januari 2021/Diterima: 11 Mac 2021

ABSTRACT

Endothelial-to-mesenchymal transition (EndoMT) is a common phenomenon in vascular diseases, while the role of endothelial dysfunction in central vascular disease remains to be further investigated. MiR-122 is an inflammation-associated non-coding RNA that participates in multiple human disease, but whether miR-122 plays as a critical role in EndoMT induced by ischaemic stroke is unknown. Although BAI2 is known as a brain-specific inhibitor protein of angiogenesis, few studies of BAI2 examined EndoMT. This study investigated the mechanism of EndoMT and the miR-122/BAI2 axis in oxygen-glucose deprivation/reperfusion (OGD/R)-mediated EndoMT. A transient middle cerebral artery occlusion (tMCAO) model and OGD/R treatment were used to mimic the ischaemia-reperfusion injury. The colocalization of CD31 and α-SMA was elevated in the peri-infarct area of tMCAO mice. The expression of miR-122 was decreased in the peri-infarct area of tMCAO mice. Downregulation of miR-122, Occludin, and ZO-1 was observed in human brain microvascular endothelial cells (HBMECs) after OGD/R treatment, while α-SMA expression was increased in HBMECs after OGD/R treatment. MiR-122 overexpression reduced the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. MiR-122 negatively regulated BAI2 expression, and OGD/R treatment enhanced BAI2 expression. Knockdown the expression of BAI2 suppressed the decrease of Occludin and ZO-1 expression and the increase of α-SMA expression induced by OGD/R. In conclusion, miR-122 overexpression attenuates OGD/R-mediated EndoMT by targeting BAI2.

Keywords: BAI2; EndoMT; miR-122; OGD/R

ABSTRAK

Peralihan endotelium-kepada-mesenkim (EndoMT) adalah fenomena biasa untuk penyakit vaskular, manakala peranan disfungsi endotelium pada penyakit vaskular pusat masih perlu dikaji lebih lanjut. MiR-122 ialah RNA bukan pengekodan yang berkaitan dengan keradangan yang menyumbang kepada pelbagai penyakit manusia, tetapi sama ada miR-122 memainkan peranan penting dalam EndoMT yang disebabkan oleh strok iskemia tidak diketahui. Walaupun BAI2 dikenali sebagai protein angiogenesis perencat khusus otak, beberapa kajian BAI2 mengkaji EndoMT. Penyelidikan ini mengkaji mekanisme EndoMT dan paksi miR-122/BAI2 dalam kekurangan oksigen-glukosa/reperfusi (OGD/R)-pengantara EndoMT. Model oklusi arteri serebrum tengah sementara (tMCAO) dan rawatan OGD/R digunakan untuk meniru kecederaan reperfusi iskemia. Kolokalisasi CD31 dan α-SMA dinaikkan di kawasan peri-infark tikus tMCAO. Pengekspresan miR-122 telah menurun di kawasan peri-infark tikus tMCAO. Pengawalaturan rendah miR-122, Occludin dan ZO-1 diperhatikan dalam sel endotelium mikrovaskular otak manusia (HBMEC) selepas rawatan OGD/R, manakala pengekspresan α-SMA meningkat dalam HBMEC selepas rawatan OGD/R. Pengekspresan berlebihan MiR-122 mengurangkan penurunan pengekspresan Occludin dan ZO-1 dan peningkatan pengekspresan α-SMA yang disebabkan oleh OGD/R. MiR-122 mengawal pengekspresan BAI2 secara negatif dan rawatan OGD/R meningkatkan pengekspresan BAI2. Pengurangan pengekspresan BAI2 menindas penurunan pengekspresan Occludin dan ZO-1 serta peningkatan pengekspresan α-SMA yang disebabkan oleh OGD/R. Kesimpulannya, pengekspresan berlebihan miR-122 melemahkan OGD/R-pengantara EndoMT dengan menyasarkan BAI2.

Kata kunci: BAI2; EndoMT; miR-122; OGD/R

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*Pengarang untuk surat-menyurat; email: ccyyzhangntfy@163.com