Aryl hydrocarbon receptor (AHR) functions in infectious and sterile inflammation and NAD+-dependent metabolic adaptation

Bock, Karl Walter

doi:10.1007/s00204-021-03134-9

Cited by 12 publications

(5 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TIPARP encodes a poly(ADP-ribose) polymerase regulating innate immunity and repressing type I interferon signaling [ 40 ]. It also modulates stem cell pluripotency, autophagy and gene expression, with induction by growth factors, viral infection, nuclear receptors, hypoxia and aryl hydrocarbon receptor (AHR) [ 41 ]. Prior studies establish TIPARP as a negative regulator of AHR and IFN-I signaling [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma

Zhang,

Zhou,

Yao

et al. 2024

Cancer Cell Int

View full text Add to dashboard Cite

Background Male patients with papillary thyroid carcinoma (PTC) tend to have poorer prognosis compared to females, partially attributable to a higher rate of lymph node metastasis (LNM). Developing a precise predictive model for LNM occurrence in male PTC patients is imperative. While preliminary predictive models exist, there is room to improve accuracy. Further research is needed to create optimized prognostic models specific to LNM prediction in male PTC cases. Methods We conducted a comprehensive search of publicly available microarray datasets to identify candidate genes continuously upregulated or downregulated during PTC progression in male patients only. Univariate Cox analysis and lasso regression were utilized to construct an 11-gene signature predictive of LNM. TIPARP emerged as a key candidate gene, which we validated at the protein level using immunohistochemical staining. A prognostic nomogram incorporating the signature and clinical factors was developed based on the TCGA cohort. Results The 11-gene signature demonstrated good discriminative performance for LNM prediction in training and validation datasets. High TIPARP expression associated with advanced stage, high T stage, and presence of LNM. A prognostic nomogram integrating the signature and clinical variables reliably stratified male PTC patients into high and low recurrence risk groups. Conclusions We identified a robust 11-gene signature and prognostic nomogram for predicting LNM occurrence in male PTC patients. We propose TIPARP as a potential contributor to inferior outcomes in males, warranting further exploration as a prognostic biomarker and immunotherapeutic target. Our study provides insights into the molecular basis for gender disparities in PTC.

show abstract

Section: Discussionmentioning

confidence: 99%

TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma

Zhang,

Zhou,

Yao

et al. 2024

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…TIPARP (a.k.a PARP7), TCDD-inducible poly [ADP-ribose] polymerase, is an ADP-ribosyltransferase that mediates the mono-ADP-ribosylation of target proteins to control gene expression. For example, it functions as a negative regulator of AHR, a ligand-activated transcription factor, to regulate biological processes such as angiogenesis, hematopoiesis, cell motility, and drug and lipid metabolism 31 , 32 . Although AHR disrupts the contact inhibition 33 , the function and mechanisms of TIPARP in the nucleus and cytoplasm are still not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin

Li,

Nakamura

2023

Sci Rep

View full text Add to dashboard Cite

The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.

show abstract

“…Mounting evidence has shown that AhR is involved in the regulation of cellular metabolism in many types of cells by acting as a TF to control the expression of metabolism-related genes, by interacting with intracellular signaling pathways related to metabolism, or by disturbing mitochondrial function 56, 57 . AhR is expressed by various immune cells, and its signaling exerts integrative effects on the cellular environment and metabolism of the immune responses 58 .…”

Section: Discussionmentioning

confidence: 99%

Uremic toxin indoxyl sulfate induces trained immunityviathe AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD)

Kim

Lee

et al. 2022

Preprint

View full text Add to dashboard Cite

Trained immunity is the long-term functional reprogramming of innate immune cells following exposure to various insults that results in altered responses towards a secondary challenge. Indoxyl sulfate (IS) is a potent uremic stimulus associated with inflammation in chronic kidney disease (CKD). However, the impact of IS on trained immunity remains unknown. Here, we find that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production upon LPS-stimulation. Further, the aryl hydrocarbon receptor contributes to IS-trained immunity by enhancing expression of arachidonic acid metabolism-related genes ALOX5 and ALOX5AP. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and healthy monocytes trained with uremic sera from ESRD patients exhibit increased TNF-α and IL-6 production. Moreover, IS-trained mice have augmented TNF-α production following LPS-stimulation. These results provide insight into the role of IS in trained immunity, which is critical during inflammatory responses in CKD patients.

show abstract

Aryl hydrocarbon receptor (AHR) functions in infectious and sterile inflammation and NAD+-dependent metabolic adaptation

Cited by 12 publications

References 97 publications

TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma

TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma

Identification and partial characterization of new cell density-dependent nucleocytoplasmic shuttling proteins and open chromatin

Uremic toxin indoxyl sulfate induces trained immunityviathe AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD)

Contact Info

Product

Resources

About