Cirrhosis of liver: Interference of serpins in quantification of SERPINA4 – A preliminary study

Nallagangula, Krishna Sumanth; Shashidhar, KN; Lakshmaiah, V; Muninarayana, C

doi:10.1016/j.plabm.2017.10.002

Cited by 12 publications

(7 citation statements)

References 25 publications

(25 reference statements)

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“…Serpina4-ps1 is a pseudogene of the serine proteinase inhibitor superfamily that originates from clade A member 4 [ 43 ]. The functional gene Serpina4 , also known as kallistatin, is abundant in the liver and a potent vasodilatory protein involved in the prevention of cardiovascular disease [ 44 ]. Recently, a case–control study [ 45 ] demonstrated that Serpina4 was down-regulated in the liver of obese NAFLD patients and plays critical roles in the inhibition of inflammation and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Early-life undernutrition induces enhancer RNA remodeling in mice liver

Wang

Mao

Zhao

et al. 2021

Epigenetics & Chromatin

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Background Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription. Results Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4 weeks and 7 weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4 weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300. Conclusions Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Early-life undernutrition induces enhancer RNA remodeling in mice liver

Wang

Mao

Zhao

et al. 2021

Epigenetics & Chromatin

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“…Serpin family A member 4 (SERPINA4), also known as kallistatin, is a novel antiangiogenesis protein, which exerts various effects on inflammation, angiogenesis and tumor growth (61,62). Previous studies reported that SERPINA4 suppressed tumor growth by directly inhibiting cancer cell proliferation, migration and invasion, and by adjusting cancer cell signaling in various malignant tumors, including lung and breast cancers, and HCC (61–63). Kallistatin levels were positively correlated with free androgen index in women with polycystic ovary syndrome (64).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of sexual dimorphism‑linked gene expression profile in hepatocellular carcinoma

Yao

Feng

et al. 2019

Oncol Rep

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Hepatocellular carcinoma (HCC) is sexually disparate in humans, with a significantly increased prevalence in males. The molecular mechanisms by which the inhibition or development of liver cancer are facilitated require further investigation with regard to sex factors affecting disease progression. In the present study, functional signatures of differentially expressed genes (DEGs) were screened in female and male tumors via bioinformatics analysis. The following gene chip expression profiles were downloaded from the Gene Expression Omnibus: GSE19665, GSE23342 and GSE9843. They comprised cancerous and non-cancerous tissue from patients with HCC and included critical sex features. Further evaluation of selected DEGs in the two sexual groups was performed via hierarchical clustering analysis. Venn diagram and functional protein-protein interaction (PPI) network analyses were performed. Survival analysis of patients with differences in gene expression levels was subsequently performed using the Kaplan-Meier Plotter database. Certain identified DEGs were common in female and male tumor samples, whereas others exhibited a sexually-biased expression profile. Gene Ontology revealed that the cell cycle module ‘biological process’ was enriched in tumors derived from both sexes, whereas the metabolic pathways and drug metabolism modules were only significantly enriched in cancer tissues from male subjects. A number of hub DEGs in the cell cycle and p53 signaling pathways were involved in significant protein-protein interaction (PPI) modules, including CDK1 and CCNB1 . These DEGs were upregulated in tumors derived from female subjects compared with those derived from male subjects, and could be used as markers of poor prognosis in male patients. Other genes, such as CYP3A4 and SERPINA4 , were identified in metabolic pathways, and were downregulated in male compared with female subjects. These genes were associated with a decreased survival rate. The data demonstrated that sex differences in physiology may regulate the levels of gene expression and/or activity, including gene function associated with oncogenesis and the outcomes of liver cancer. Additional surveys are required to explore in detail the molecular mechanisms underlying the differences in gene expression between the two sexes during the development of liver cancer.

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“…Primary antibodies (polyclonal and monospecific antibodies separately) were diluted (1:100) and PVDF membranes were incubated in diluted primary antibody solution at room temperature with slow shaking on rocker for 2 to 3 hours. PVDF membranes were washed with 1x PBST thrice for 3 minutes each [15,16].…”

Section: Western Blotmentioning

confidence: 99%

Cirrhosis of liver: Comparative cross reactivity for quantification of SERPINA4/Kallistatin

Nallagangula¹

2021

JCLR

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Cirrhosis of liver is an end stage of chronic liver insults from varied etiologies which leads to impaired liver functions. Proteins expressed from liver and enters into circulation reflects degree of liver dysfunction. Serpins (Serine protease inhibitors) are class of plasma proteins expressed from liver; SERPINA4/Kallistatin is a multifunctional serpin clade A protein expressed from liver and concentration in serum is the reflection of extent of liver dysfunction. The present study aimed to compare cross reactivity of serpins for polyclonal and monospecific antibodies in both cirrhotic liver and healthy subjects. Blood samples were collected from 20 subjects (10 cirrhotic liver, 10 healthy) from R. L. Jalappa Hospital and Research Centre, Kolar, Karnataka, India. Separation of proteins was carried out by SDS-PAGE. Cross reactivity study was analyzed using western blot. Proteins present in cirrhotic liver and healthy subject’s serum were separated by SDS PAGE. There was no band detection on both (cirrhotic liver and healthy) PVDF (polyvinylidene diflouride) membranes with polyclonal antibodies. However, a significant band was observed with protein of interest in healthy PVDF membrane with monospecific antibodies. There was no band in cirrhotic liver PVDF membrane even with monospecific antibodies. Comparative cross reactivity analysis of serpins in quantification of SERPINA4/Kallistatin in the present study demonstrated that there will not be any immunological cross reactivity between serpins and SERPINA4/Kallistatin due to the absence of identical epitope in cirrhotic liver and healthy subjects.

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Cirrhosis of liver: Interference of serpins in quantification of SERPINA4 – A preliminary study

Cited by 12 publications

References 25 publications

Early-life undernutrition induces enhancer RNA remodeling in mice liver

Early-life undernutrition induces enhancer RNA remodeling in mice liver

Identification and characterization of sexual dimorphism‑linked gene expression profile in hepatocellular carcinoma

Cirrhosis of liver: Comparative cross reactivity for quantification of SERPINA4/Kallistatin

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