Overexpression of translocator protein in inflammatory bowel disease: Potential diagnostic and treatment value

Ostuni, Mariano A.; Issop, Leeyah; Péranzi, Gabriel; Walker, Francine; Fasseu, Magali; Elbim, Carole; Papadopoulos, Vassilios; Lacapère, J

doi:10.1002/ibd.21250

Cited by 34 publications

(37 citation statements)

References 47 publications

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“…This would suggest that infiltrating macrophages with elevated TSPO expression are present in these parts on the intestinal tract. This observation is in agreement with studies showing elevated TSPO expression in biopsies from patients with chronic IBD and in tissue sections from the descending colon of animals subjected to chemically induced colitis [29, 40]. …”

Section: Discussionsupporting

confidence: 92%

“…In the mitochondrial membrane of activated macrophages, the expression of 18-kDa translocator protein (TSPO) receptors is strongly increased [27, 28]. In fact, high levels of TSPO receptors were observed in the colon of patients with IBD and in animal models of colitis [29, 40]. Therefore, the TSPO receptor could be a suitable biomarker to monitor colitis-related intestinal inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis

et al. 2016

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PurposeUlcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [11C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated.ProceduresColitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [11C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [11C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation.ResultsEleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [11C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [11C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11.ConclusionInflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [11C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis

et al. 2016

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“…In both MEFs and CF35, TSPO exhibited a mitochondrial pattern, visualized by discrete colocalization with VDAC1 consistent with previous studies. 41,46 Consequently, we sought to alter the ratio of TSPO:VDAC1 expression by transiently knocking down TSPO with siRNA (-TSPO) or overexpressing with cDNA (CTSPO). Cells transfected with an empty vector (C) or a nonsilencing siRNA (NSC) were used as controls.…”

Section: Resultsmentioning

confidence: 99%

TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control

et al. 2014

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The 18-kDa TSPO (translocator protein) localizes on the outer mitochondrial membrane (OMM) and participates in cholesterol transport. Here, we report that TSPO inhibits mitochondrial autophagy downstream of the PINK1-PARK2 pathway, preventing essential ubiquitination of proteins. TSPO abolishes mitochondrial relocation of SQSTM1/p62 (sequestosome 1), and consequently that of the autophagic marker LC3 (microtubule-associated protein 1 light chain 3), thus leading to an accumulation of dysfunctional mitochondria, altering the appearance of the network. Independent of cholesterol regulation, the modulation of mitophagy by TSPO is instead dependent on VDAC1 (voltagedependent anion channel 1), to which TSPO binds, reducing mitochondrial coupling and promoting an overproduction of reactive oxygen species (ROS) that counteracts PARK2-mediated ubiquitination of proteins. These data identify TSPO as a novel element in the regulation of mitochondrial quality control by autophagy, and demonstrate the importance for cell homeostasis of its expression ratio with VDAC1.

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“…Paraffin sections (3 mm) were rehydrated and then stained with H&P-Saffron. The percentages of lesions were evaluated by a semi-morphoquantitative method described by Otsuni et al 45 …”

Section: Histopathology Of the Distal Colonmentioning

confidence: 99%

Beneficial Effects of an Amino Acid Mixture on Colonic Mucosal Healing in Rats

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Beaumont

Walker

et al. 2013

Inflammatory Bowel Diseases

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Overexpression of translocator protein in inflammatory bowel disease: Potential diagnostic and treatment value

Cited by 34 publications

References 47 publications

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis

TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control

Beneficial Effects of an Amino Acid Mixture on Colonic Mucosal Healing in Rats

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