Augmenter of liver regeneration (ALR) crotonylation assists in mitochondria-ER contact to alleviate hepatic steatosis.

Background & Aims: Crotonylation (Kcr), a newly identified post-translation modification (PTM), has been confirmed to be involved in diverse biological processes and human diseases as well. Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a serious threat to people's health. Augmenter of liver regeneration (ALR) is an important liver regulatory protein, and the insufficiency of ALR expression is reported to accelerate liver steatosis progression to liver fibrosis or even hepatic carcinoma (HCC).

Lack of Augmenter of Liver Regeneration Disrupts Cholesterol Homeostasis of Liver in Mice by Inhibiting the AMPK Pathway.

It is well known that excessive cholesterol accumulation within hepatocytes deteriorates nonalcoholic fatty liver disease (NAFLD). Augmenter of liver regeneration (ALR) has been reported to alleviate NAFLD through anti-apoptosis; however, whether ALR could protect liver from cholesterol-induced NAFLD remains unclear. Mice with heterozygous deletion of (the gene for ALR, ) were generated, and liver steatosis was induced by either choline-deficient ethionine-supplemented, methionine choline-deficient diet for 4 weeks, or high-fat diet for 16 weeks.

Overexpression of the immediate early response 5 gene increases the radiosensitivity of HeLa cells.

The effects of the immediate early response 5 () gene on the sensitivity of HeLa cells to radiation remain unclear. In the present study, stably transfected HeLa cells resulting in the knockdown or overexpression of were investigated. In addition, xenografts of normal, -silenced and -overexpressed HeLa cells were injected into nude mice and examined.

Differential composition of gut microbiota among healthy volunteers, morbidly obese patients and post-bariatric surgery patients.

The modulation of the gut microbiota was recently deemed one of the mechanisms responsible for the excellent outcomes of bariatric surgery. However, to date, only few studies have assessed this, and they have high heterogeneity. In the present study, next-generation 16S ribosomal DNA amplicon sequencing was used to characterize the gut microbiota of healthy volunteers, as well as patients prior to and after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).

Deficiency in augmenter of liver regeneration accelerates liver fibrosis by promoting migration of hepatic stellate cell.

Background: Augmenter of liver regeneration (ALR) protects liver from various injuries, however, the association of ALR with liver fibrosis, particularly its effect on hepatic stellate cells (HSC), remains unclear. In this study, we investigated the impact of ALR on the activation of HSC, a pivotal event in occurrence of liver fibrosis.

Methods: Liver fibrosis was induced in vivo in mice with heterozygous ALR knockdown (ALR-KD) by administration of CCl or bile duct ligation.

Lack of hepatic stimulator substance expression promotes hepatocellular carcinoma metastasis partly through ERK-activated epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to its high frequency of metastasis via the epithelial-mesenchymal transition (EMT) pathway. Hepatic stimulator substance (HSS) can protect hepatocytes from injury and promote liver growth. Recent studies indicated that HSS expression is increased in HCC tissues; however, whether HSS expression is potentially associated with HCC metastasis, particularly through the EMT pathway, remains largely unknown.

Deceleration of liver regeneration by knockdown of augmenter of liver regeneration gene is associated with impairment of mitochondrial DNA synthesis in mice.

Hepatic stimulator substance, also known as augmenter of liver regeneration (ALR), is a novel hepatic mitogen that stimulates liver regeneration after partial hepatectomy (PH). Recent work has indicated that a lack of ALR expression inhibited liver regeneration in rats, and the mechanism seems to be related to increased cell apoptosis. The mitochondria play an important role during liver regeneration.

Involvement of hepatic stimulator substance in the regulation of hepatoblast maturation into hepatocytes in vitro.

Hepatic stimulator substance (HSS), also known as augmenter of liver regeneration (ALR), acts as a hepatotrophic growth factor to promote liver regeneration after liver damage or partial hepatectomy. However, the expression and function of HSS during liver development in mammals remain largely unknown. In this work, the hepatoblasts were isolated from mice at embryonic day 13.

Downregulation of hepatic stimulator substance during the early phase of liver regeneration inhibits E-cadherin expression in mice.

Hepatic stimulatory substance (HSS), which encodes a sulfhydryl oxidase enzyme, promotes liver regeneration (LR) and maintains the viability of hepatocytes. Surprisingly, we found that the levels of the HSS mRNA and expressed protein were both strongly repressed at 12h after a 70% partial hepatectomy (PH) in mice. Understanding the mechanism and effect of this extraordinary suppression can provide a novel path for exploring the molecular function of HSS during LR.

Epidermal growth factor down-regulates the expression of human hepatic stimulator substance via CCAAT/enhancer-binding protein β in HepG2 cells.

hHSS (human hepatic stimulator substance), acting as a hepatotrophic growth factor, promotes liver regeneration. However, the regulatory mechanisms for hHSS transcription are still poorly understood. In the present study, we investigated transcription of hHSS triggered by EGF (epidermal growth factor) and the role of C/EBPβ (CCAAT/enhancer-binding protein β) as a potential core factor responsible for hHSS transcription in HepG2 cells.

Increased hepatic UCP2 expression in rats with nonalcoholic steatohepatitis is associated with upregulation of Sp1 binding to its motif within the proximal promoter region.

Uncoupling protein-2 (UCP2) is a mitochondrial inner-membrane carrier protein that is involved in the control of fatty acid metabolism. To understand the mechanism of the transcriptional regulation of ucp2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), we cloned 500 bp upstream of the ucp2 exon 1 from a rat liver cDNA library and identified cis-acting regulatory elements. The transcriptional start site was identified as "C," -359 bp from the ATG codon.

Down-regulation of hepatic nuclear factor 4alpha on expression of human hepatic stimulator substance via its action on the proximal promoter in HepG2 cells.

hHSS (human hepatic stimulator substance) stimulates hepatocyte growth. To understand the mechanism controlling hHSS expression, we analysed the proximal promoter activity and identified two regulatory regions (-212/-192 and -152/-132) that were important for transcription in HepG2 cells. Using the luciferase reporter assay, gel-shift experiments and ChIP (chromatin immunoprecipitation), we found that the transcription factors HNF4alpha (hepatocyte nuclear factor 4alpha) and Sp1 (stimulating protein-1) were essential for hHSS promoter activity and could directly bind to regions -209/-204 and -152/-145 respectively.

Identification of human hepatic stimulator substance gene promoter and demonstration of dual regulation of AP1/AP4 cis-acting element in different cell lines.

Human hepatic stimulator substance (hHSS) is a newly identified growth-promoting factor in the liver. HSS is capable of stimulating hepatic regeneration in partial hepatectomized rats, thus, promoting growth of hepatic tumor cells. To understand and elucidate the transcriptional regulation of hHSS gene, the 4890bp of 5'-flanking region of the gene have been isolated and sequenced.

[Distribution and significance of cSNP in KCNA7 gene as a novel NIDDM candidate gene in the population of northeast China].

To investigate the distribution and significance of a coding single nucleotide polymorphism (cSNP) of the novel NIDDM candidate gene,KCNA7 in the population of Northeast China, 97 patients with NIDDM and 141 controls were tested. Genotypes of KCNA7 gene T418M(C/T) were performed by PCR-RFLP, and SSCP was used to detect other unknown variations near the C/T site of KCNA7 gene. As a result, no significant difference was observed in the distribution of genotypes of T418M(C/T) between NIDDM and control group.

[Effect of the regulation of IGFs system components in retinoic acid-induced congenital clubfoot].

The fetal rat models with congenital clubfoot were constructed by treating 24 Wistar rats with all trans retinoic acid (ATRA). The MC-3T3-E1 cells were cultured with ATRA, 17 beta-estrogen (E2) or combinations of the two chemicals. The flow cytometer was used to determine the cell proliferation.

[Antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gene expression of insulin-like growth factors family in osteoblast cells].

Objective: To investigate the antiestrogenic effect of environment teratogen on the gene expression of insulin-like growth factors (IGFs) family in osteoblast cells during rat skeleton development.

Methods: The fetal rat models with congenital skeleton malformation were constructed by treating 20 female Wistar rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pregnant day 10. The MC-3T3-E1 cells were cultured with estrogen, TCDD, or a combination of the two chemicals for 24 hours.

[Correlation analysis between WNK4 gene and essential hypertension].

Objective: To investigate association of mutation in WNK4 gene with essential hypertension and to analyze the expression of WNK4 gene.

Methods: cSNP in WNK4 gene in a small samples was detected by sequencing, then PCR-RFLP was performed in 98 patients with essential hypertension and 95 control subjects. The expression profile of WNK4 gene was tested by RT-PCR.

[Cloning and analysis of human alpha-1B glycoprotein precursor gene: a novel member of human immunoglobulin superfamily].

A cDNA of 1694 bp was cloned from human liver Marathon cDNA by means of Rapid Amplification of cDNA Ends (RACE). The cDNA has an open reading frame at 43-1530 bp encoding 495 amino acid residues and a 17-residue signal peptide. There are four Igc2 domains in the translated polypeptide, which is highly homologous to the human alpha-1B glycoprotein isolated from human plasma.

[Polymorphism analysis of 825C/T of the G-protein beta 3 subunit in high risk population of hypertension in the northeast China].

PCR-RFLP was used for genotyping of GNB3 C/T in 133 patients with EH and 257 healthy control subjects in the high risk population and in 98 patients with EH and 110 healthy control subjects in general population. Some biochemical tests were performed also. The association between the polymorphism and blood pressure was analyzed by the case-control study.