Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review

Li, Meihui; Liu, Shengnan; Huang, Wei; Zhang, Junjie

doi:10.18632/aging.203147

Cited by 9 publications

(7 citation statements)

References 105 publications

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“…Crystallin gamma D has a very similar sequence and structure to that of crystallin beta, but it is monomeric [55]. While there are no clear attributed functions of gamma-crystallin in ovaries, beta-crystallin does in uence female fertility by regulating apoptosis in granulosa cells and follicular atresia [55]. Hence, downregulation of CRYGD may be consistent with alterations of the menstrual cycle observed in women recovering from COVID-19 [37].…”

Section: Discussionmentioning

confidence: 84%

“…In fact, infected ovaries exhibited downregulation of crystallin gamma D (CRYGD) and upregulation of the 5hydroxytryptamine (serotonin) receptor 1A (HTR1A) gene. Crystallin gamma D has a very similar sequence and structure to that of crystallin beta, but it is monomeric [55]. While there are no clear attributed functions of gamma-crystallin in ovaries, beta-crystallin does in uence female fertility by regulating apoptosis in granulosa cells and follicular atresia [55].…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional changes of tissue-specific genes in multiple endocrine organs: a study of lethal COVID-19 cases

Poma

Bonuccelli

Macerola

et al. 2022

Preprint

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Altered blood hormone and metabolite levels during and post-COVID-19 have been extensively reported. Yet, studies of gene expression at the tissue level that can help identify the causes of endocrine dysfunctions are scarce. We analyzed transcript levels of endocrine-specific genes in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 and 27 uninfected controls) were included. All samples were tested for SARS-CoV-2 genome. Investigated organs included adrenals, pancreas, ovary, thyroid and white adipose tissue (WAT). Transcript levels of 42 endocrine-specific and 3 IFN-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in tissue) and uninfected controls. ISG transcript levels were enhanced in tissues positive for SARS-CoV-2. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of ovary, pancreas and thyroid but enhanced in adrenals. In WAT of COVID-19 cases transcription of ISGs and leptin was enhanced independently of the presence of virus. Our findings suggest that, in COVID-19, endocrine dysfunctions may arise especially when SARS-CoV-2 invades endocrine organs and that transcriptional alterations of endocrine-specific genes may contribute to endocrine manifestations.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Transcriptional changes of tissue-specific genes in multiple endocrine organs: a study of lethal COVID-19 cases

Poma

Bonuccelli

Macerola

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Apparently, a controversial scenario was detected in ovaries positive for SARS-CoV-2: downregulation of crystallin gamma D ( CRYGD ) and upregulation of the 5-hydroxytryptamine (serotonin) receptor 1A ( HTR1A ) gene. By sequence and structure, crystallin gamma D is similar to crystallin beta, but the latter is monomeric [ 37 ]. Currently, no clear functions have been attributed to gamma-crystallin in ovaries, but beta-crystallin does influence female fertility by regulating apoptosis in granulosa cells and follicular atresia [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…By sequence and structure, crystallin gamma D is similar to crystallin beta, but the latter is monomeric [ 37 ]. Currently, no clear functions have been attributed to gamma-crystallin in ovaries, but beta-crystallin does influence female fertility by regulating apoptosis in granulosa cells and follicular atresia [ 37 ]. Hence, the downregulation of CRYGD may be consistent with alterations of the menstrual cycle observed in women recovering from COVID-19 [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19

et al. 2023

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Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. Key messages • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.

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“…The rest group of genes that were significantly upregulated in HIF-2-altered tumors are involved in urothelial differentiation ( UPK2 ) [ 33 ], stemness ( GPR78, HS3ST2 ) [ 34 , 35 ], epithelial-mesenchymal transition (CRYBG2) [ 36 ], PI3K/Akt/beta-catenin signaling ( VGLL1 ) [ 37 ], MAPK signaling (SH3TC2, GAREM1) [ 38 , 39 ], coactivation of different nuclear receptors ( NCOA1 ) [ 40 ], ER stress and hedgehog signaling ( CREB3L2 ) [ 41 ], TGF-beta and WNT signaling (CRYBG2) [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

et al. 2022

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Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-preventing genes.

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Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review

Cited by 9 publications

References 105 publications

Transcriptional changes of tissue-specific genes in multiple endocrine organs: a study of lethal COVID-19 cases

Transcriptional changes of tissue-specific genes in multiple endocrine organs: a study of lethal COVID-19 cases

Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

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