Dysfunctional Nurr1 promotes high glucose-induced Müller cell activation by up-regulating the NF-κB/NLRP3 inflammasome axis

Li, Wendie; Liu, Xiaojuan; Tu, Yuanyuan; Ding, Daofang; Qian, Yi; Sun, Xiaolei; Wang, Yanyan; Wang, Kun; Zhu, Manhui; Mao, Jinghai

doi:10.1016/j.npep.2020.102057

Cited by 31 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this, other studies reported that direct intraperitoneal injection of glucose in rodents also increased hypothalamic Il-1α, Il-1β mRNA and prostaglandins (PG) level [3,88]. Additionally, in vitro studies have shown that primary cultures of microglia, astrocytes, or Muller glial cells exposed to high glucose conditions exhibited increased production of inflammatory cytokines and reactive oxygen species (ROS) via activation of inflammatory signaling pathways [28,[89][90][91]. It is also found that incubation of hypothalamic explants at high glucose concentration also increased the levels of Il-1α, Il-1β, and Tnfα mRNA [28,88].…”

Section: B Hyperglycemiamentioning

confidence: 66%

Hypothalamic inflammation in metabolic disorders and aging

Bhusal

Rahman

Suk

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The hypothalamus is a critical brain region for the regulation of energy homeostasis. Over the years, studies on energy metabolism primarily focused on the neuronal component of the hypothalamus. Studies have recently uncovered the vital role of glial cells as an additional player in energy balance regulation. However, their inflammatory activation under metabolic stress condition contributes to various metabolic diseases. The recruitment of monocytes and macrophages in the hypothalamus helps sustain such inflammation and worsens the disease state. Neurons were found to actively participate in hypothalamic inflammatory response by transmitting signals to the surrounding non-neuronal cells. This activation of different cell types in the hypothalamus leads to chronic, low-grade inflammation, impairing energy balance and contributing to defective feeding habits, thermogenesis, and insulin and leptin signaling, eventually leading to metabolic disorders (i.e., diabetes, obesity, and hypertension). The hypothalamus is also responsible for the causation of systemic aging under metabolic stress. A better understanding of the multiple factors contributing to hypothalamic inflammation, the role of the different hypothalamic cells, and their crosstalks may help identify new therapeutic targets. In this review, we focus on the role of glial cells in establishing a cause-effect relationship between hypothalamic inflammation and the development of metabolic diseases. We also cover the role of other cell types and discuss the possibilities and challenges of targeting hypothalamic inflammation as a valid therapeutic approach.

show abstract

Section: B Hyperglycemiamentioning

confidence: 66%

Hypothalamic inflammation in metabolic disorders and aging

Bhusal

Rahman

Suk

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…223 Nuclear receptor related 1 (Nurr1/ NR4A2) ameliorates the activation of Müller cells and the cell death of retinal ganglion cells in a diabetes model through suppression of NF-κB action and inhibition of NLRP3 inflammasome component expression, such as NLRP3 and ASC. 224 However, some nuclear receptors may function in the activation of the NLRP3 inflammasome. All-trans-retinoic acid, a derivative of vitamin A, induces the expression of NLRP3 and pro-IL-1β at the priming step and promotes activation of the NLRP3 inflammasome by inducing human macrophages to undergo glycolysis.…”

Section: Dual Regulatory Mechanisms Controlling the Nlrp3 Inflammasomementioning

confidence: 99%

An update on the regulatory mechanisms of NLRP3 inflammasome activation

et al. 2021

View full text Add to dashboard Cite

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.

show abstract

“…NLRP3 inflammasome is a protein complex in the innate immune system that recognizes pathogen- and danger-associated molecular patterns, which is composed of NLRP3, ASC and caspase-1( 34 ). Activation of the NF-κB/NLRP3 inflammasome signaling serves a key role in the progression of DR ( 19 , 20 , 35-38 ). In the present study, it was observed that nesfatin-1 reduced the protein levels of NF-κB, NLRP3, ASC and caspase-1, and inhibited the activation of the NF-κB/NLRP3 inflammasome signaling following high glucose stimulation.…”

Section: Discussionmentioning

confidence: 99%

Protective role and molecular mechanism of action of Nesfatin‑1 against high glucose‑induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

et al. 2021

View full text Add to dashboard Cite

Diabetic retinopathy (DR) is a major complication of diabetes mellitus that may cause severe visual impairment. It has been reported that the levels of nesfatin-1 in the serum and vitreous humor were negatively correlated with DR; however, its role in DR has not been fully elucidated. Therefore, the present study was performed to investigate the effect of nesfatin-1 on high glucose-treated human retinal epithelial cells (ARPE-19) and explore the underlying mechanism. The effects of nesfatin-1 on cell viability, inflammation, oxidative stress and apoptosis were examined under high glucose conditions. The Cell Counting Kit-8 assay was used to determine cell viability. The levels of inflammatory cytokines were evaluated using ELISA kits. The reactive oxygen species and malondialdehyde content was estimated using commercial assay kits. Flow cytometry was performed to detect apoptotic cells and western blot analysis was employed to evaluate the expression of apoptosis-associated proteins. Moreover, the levels of NF-κB, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and high-mobility group protein B1 (HMGB1) were determined via western blot analysis. The results revealed that nesfatin-1 enhanced cell viability and suppressed inflammation, oxidative stress and apoptosis in the presence of high glucose concentration. Moreover, the activation of the NF-κB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin-1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF-κB/NLRP3 inflammasome pathway caused by nesfatin-1. Taken together, these findings demonstrated that nesfatin-1 inhibited the activation of the NF-κB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE-19 cells against high glucose-induced inflammation, oxidative stress and apoptosis.

show abstract

Dysfunctional Nurr1 promotes high glucose-induced Müller cell activation by up-regulating the NF-κB/NLRP3 inflammasome axis

Cited by 31 publications

References 35 publications

Hypothalamic inflammation in metabolic disorders and aging

Hypothalamic inflammation in metabolic disorders and aging

An update on the regulatory mechanisms of NLRP3 inflammasome activation

Protective role and molecular mechanism of action of Nesfatin‑1 against high glucose‑induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

Contact Info

Product

Resources

About