Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury

Fan, Zu-Yan; Gao, Yan; Jiang, Nan; Zhang, Fengxia; Liu, Shuangxin; Li, Quhuan

doi:10.3389/fimmu.2022.979995

Cited by 7 publications

(9 citation statements)

References 33 publications

(37 reference statements)

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“…Studies have suggested that Spi2a contributes to memory T cell development, controls the viability of Th2 cells, and mediates B-cell and granulocyte formation 34 – 37 . SERPINA3 , the human orthologue of Spi 2a , is also identified to be an inflammation-related gene and closely associated with immune responses 38 , 39 . However, the function of Spi2a in macrophages in the context of sepsis remains elusive.…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice

Wang

Ding

et al. 2023

Nat Commun

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Bacteria-triggered sepsis is characterized by systemic, uncontrolled inflammation in affected individuals. Controlling the excessive production of pro-inflammatory cytokines and subsequent organ dysfunction in sepsis remains challenging. Here, we demonstrate that Spi2a upregulation in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages reduces the production of pro-inflammatory cytokines and myocardial impairment. In addition, exposure to LPS upregulates the lysine acetyltransferase, KAT2B, to promote METTL14 protein stability through acetylation at K398, leading to the increased m6A methylation of Spi2a in macrophages. m6A-methylated Spi2a directly binds to IKKβ to impair IKK complex formation and inactivate the NF-κB pathway. The loss of m6A methylation in macrophages aggravates cytokine production and myocardial damage in mice under septic conditions, whereas forced expression of Spi2a reverses this phenotype. In septic patients, the mRNA expression levels of the human orthologue SERPINA3 negatively correlates with those of the cytokines, TNF, IL-6, IL-1β and IFNγ. Altogether, these findings suggest that m6A methylation of Spi2a negatively regulates macrophage activation in the context of sepsis.

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Section: Introductionmentioning

confidence: 99%

N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice

Wang

Ding

et al. 2023

Nat Commun

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“…Serine protease inhibitor A family member 3 (SERPINA3) acts primarily as a protease inhibitor and plays an important role in the regulation of cellular processes such as oxidative stress, fibrosis, angiogenesis, inflammatory response and apoptosis ( 46 , 47 ) In diabetic nephropathy, immune-related SERPINA3 inhibits mast cell proliferation and activation by downregulating chymase activity, thereby alleviating disease progression ( 48 ). During tumor progression, STAT3-dependent SERPINA3 enhances tumor cell invasion, migration, and angiogenesis ( 46 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study

Zeng

Zuo

et al. 2023

Front. Immunol.

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PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

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“…ClusterProfile in R was used for GO analysis, and only items with p < 0.05 were considered significantly enriched. (Fan et al 2022)…”

Section: Methodsmentioning

confidence: 99%

A single-cell transcriptome analysis and prognostic model construction of stromal cells for renal cell carcinoma

Liao,

Wang,

Liu

et al. 2023

Preprint

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Renal cell carcinoma (RCC) is among the top three cancers of the urinary system and its incidence keeps increasing worldwide in recent decades. However, methods for accurate prognosis evaluation and effective treatment are still lacking nowadays. Here, to explore the molecular expression features of RCC and establish a new RCC clinical prognosis evaluation model, a cell landscape of 187,263 renal cells obtained from eight patients with RCC was analyzed in this study. And by extracting and focusing on the main stromal cells from RCC tissues, innovative molecular characteristics and pathways of tumors were identified, like the well-known hypoxia pathway. By analyzing cell-cell communication, fibroblasts were found to promote tumor development by repressing natural killer cells. Based on Cox and least absolute shrinkage and selection operator regression analysis, four risk factors were screened and used to construct a reliable RCC clinical risk estimation model. In conclusion, our work provides new insights into the tumor microenvironment of RCC, as well as potential therapeutic targets and a clinical risk model for RCC invasiveness. Hopefully, these findings will be useful for cancer research and clinical treatment in future.

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Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury

Cited by 7 publications

References 33 publications

N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice

N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study

A single-cell transcriptome analysis and prognostic model construction of stromal cells for renal cell carcinoma

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