Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.
2018
Аутори:
Jovanović Stojanov, SofijaMartinović, Vesna
Bogojević, Desanka
Poznanović, Goran
Petrović, Anja
Ivanović Matić, Svetlana
Grigorov, Ilijana
Тип документа:
Чланак у часопису (Објављена верзија)
,
© University of Navarra 2018
Метаподаци
Приказ свих података о документуАпстракт:
Chronic inflammation plays an essential role in the development of diabetic complications. Understanding the molecular mechanisms that support inflammation is a prerequisite for the design of novel anti-inflammatory therapies. These would take into consideration circulating levels of cytokines and damage-associated molecular patterns (DAMPs) that include the high mobility group box 1 (HMGB1) protein which, in part, promotes the inflammatory response through TLR4 signaling. The liver, as the source of circulating cytokines and acute-phase proteins, contributes to the control of systemic inflammation. We previously found that liver injury in streptozotocin-induced diabetic rats correlated with the level of oxidative stress, increased expression of HMGB1, and with the activation of TLR4-mediated cell death pathways. In the present work, we examined the effects of ethyl pyruvate (EP), an inhibitor of HMGB1 release/expression, on the modulation of activation of the HMGB1/TLR4 inflammatory cascade in diabetic liver. We observed that increased expression of inflammatory markers, TNF-α, IL-6, and haptoglobin in diabetic liver was associated with increased HMGB1/TLR4 interaction, activation of MAPK (p38, ERK, JNK)/NF-κB p65 and JAK1/STAT3 signaling pathways, and with decreased expression of Nrf2-regulated antioxidative enzymes. The reduction in HMGB1 expression as the result of EP administration reduced the pro-inflammatory activity of HMGB1 and exerted a protective effect on diabetic liver, which was observed as improved liver histology and antioxidant and inflammatory statuses. Our results suggest that prevention of HMGB1 release and blockage of the HMGB/TLR4 axis represents a potentially effective therapeutic strategy aimed at ameliorating diabetes-induced inflammation and ensuing liver injury.
Кључне речи:
Diabetes; Ethyl pyruvate; HMGB1/TLR4 signaling; Inflammatory response; LiverИзвор:
Journal of Physiology and Biochemistry, 2018, 74, 2, 345-358Финансирање / пројекти:
- Сигнални молекули у дијабетесу: идентификација потенцијалних биолошких маркера укључених у модификацију и интеграцију сигналних путева у циљу предикције и интервенције у дијабетесу (RS-MESTD-Basic Research (BR or ON)-173020)
DOI: 10.1007/s13105-018-0626-0
ISSN: 1138-7548
PubMed: 29611132
WoS: 000433223400014
Scopus: 2-s2.0-85044728801
URI
http://link.springer.com/10.1007/s13105-018-0626-0http://www.ncbi.nlm.nih.gov/pubmed/29611132
https://radar.ibiss.bg.ac.rs/handle/123456789/3068