E3 Ubiquitin Ligase Midline 1 Regulates Endothelial Cell ICAM-1 Expression and Neutrophil Adhesion in Abdominal Sepsis
(2023) In International Journal of Molecular Sciences 24(1).- Abstract
Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased... (More)
Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased PP2Ac levels in endothelial cells in vitro, which was reversed in endothelial cells pretreated with siRNA directed against Mid1. Thus, our novel data show that Mid1 is an important regulator of ICAM-1 expression and neutrophil adhesion in vitro and septic lung injury in vivo. A possible target of Mid1 is PP2Ac in endothelial cells. Targeting the Mid1-PP2Ac axis may be a useful way to reduce pathological lung inflammation in abdominal sepsis.
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- author
- Du, Feifei LU ; Hawez, Avin LU ; Ding, Zhiyi LU ; Wang, Yongzhi LU ; Rönnow, Carl Fredrik LU ; Rahman, Milladur LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- adhesion, endothelial cells, lung, Midline 1, sepsis
- in
- International Journal of Molecular Sciences
- volume
- 24
- issue
- 1
- article number
- 705
- publisher
- MDPI AG
- external identifiers
-
- pmid:36614145
- scopus:85146047099
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms24010705
- language
- English
- LU publication?
- yes
- id
- 7a602718-6ffc-4acc-9bbe-f120490d141b
- date added to LUP
- 2023-02-16 15:21:03
- date last changed
- 2024-09-15 19:06:42
@article{7a602718-6ffc-4acc-9bbe-f120490d141b, abstract = {{<p>Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased PP2Ac levels in endothelial cells in vitro, which was reversed in endothelial cells pretreated with siRNA directed against Mid1. Thus, our novel data show that Mid1 is an important regulator of ICAM-1 expression and neutrophil adhesion in vitro and septic lung injury in vivo. A possible target of Mid1 is PP2Ac in endothelial cells. Targeting the Mid1-PP2Ac axis may be a useful way to reduce pathological lung inflammation in abdominal sepsis.</p>}}, author = {{Du, Feifei and Hawez, Avin and Ding, Zhiyi and Wang, Yongzhi and Rönnow, Carl Fredrik and Rahman, Milladur and Thorlacius, Henrik}}, issn = {{1661-6596}}, keywords = {{adhesion; endothelial cells; lung; Midline 1; sepsis}}, language = {{eng}}, number = {{1}}, publisher = {{MDPI AG}}, series = {{International Journal of Molecular Sciences}}, title = {{E3 Ubiquitin Ligase Midline 1 Regulates Endothelial Cell ICAM-1 Expression and Neutrophil Adhesion in Abdominal Sepsis}}, url = {{http://dx.doi.org/10.3390/ijms24010705}}, doi = {{10.3390/ijms24010705}}, volume = {{24}}, year = {{2023}}, }