Exposing the Two Contrasting Faces of STAT2 in Inflammation

Duodu, Philip; Sosa, Geohaira; Canar, Jorge; Chhugani, Olivia; Gamero, Ana M.

doi:10.1089/jir.2022.0117

Cited by 5 publications

(2 citation statements)

References 141 publications

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“…Multiple stages of necroptosis and apoptosis signaling cascades can be regulated by each other. As the necroptosis-associated genes such as XIAP , TRAF2 , TRAF5 , STAT1 , STAT2 , STAT3 , STAT4 , JAK2 , BIRC3 , BIRC5 , and BIRC6 are upregulated in the patient organoids, this might imply reduced apoptosis but increased inflammatory response due to necroptosis compared to the healthy organoids [ 67 , 68 , 69 , 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome

Pranty,

Wruck,

Adjaye

2023

Cells

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Bilirubin-induced neurological damage (BIND), which might progress to kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus enabling albumin-unbound free bilirubin (BF) to cross the blood–brain barrier and accumulate within. A defect in the UGT1A1 enzyme-encoding gene, which is directly responsible for bilirubin conjugation, can cause Crigler–Najjar syndrome (CNS) and Gilbert’s syndrome. We used human-induced pluripotent stem cell (hiPSC)-derived 3D brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of BF in the developing human brain. Healthy and patient-derived iPSCs were differentiated into day-20 brain organoids, and then stimulated with 200 nM BF. Analyses at 24 and 72 h post-treatment point to BF-induced neuro-inflammation in both cell lines. Transcriptome, associated KEGG, and Gene Ontology analyses unveiled the activation of distinct inflammatory pathways, such as cytokine–cytokine receptor interaction, MAPK signaling, and NFκB activation. Furthermore, the mRNA expression and secretome analysis confirmed an upregulation of pro-inflammatory cytokines such as IL-6 and IL-8 upon BF stimulation. This novel study has provided insights into how a human iPSC-derived 3D brain organoid model can serve as a prospective platform for studying the etiology of BIND kernicterus.

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Section: Discussionmentioning

confidence: 99%

Free Bilirubin Induces Neuro-Inflammation in an Induced Pluripotent Stem Cell-Derived Cortical Organoid Model of Crigler-Najjar Syndrome

Pranty,

Wruck,

Adjaye

2023

Cells

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“…These discoveries indicate that a dysregulated immune system may play a major role in the process of pathogenesis of psoriasis. [2,3].…”

Section: Introductionmentioning

confidence: 99%

Comorbid Conditions in Psoriasis

2023

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Psoriasis is a chronic dermatosis of a multifactorial nature with a dominant role in the development of genetic factors, characterized by hyperproliferation of epidermal cells, impaired keratinization, and inflammation in the dermis. Currently, its prevalence in the population is from 0.1 to 7%, and among people hospitalized in dermatological hospitals – from 25 to 40%. In the scientific literature, the issue of considering psoriasis as a systemic disease is widely discussed, which includes damage not only to the skin, but also to other organs and systems. Thus, the indicated problems of combined pathology are relevant, require further in-depth study and search for evidence-based solutions that will improve the quality of medical care for patients with both psoriasis alone and its combined course.

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