A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1

Abstract Background Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR genes polymorphisms with disease susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs), as a new type of molecular markers developed recently, have great potential in population genetics and quantitative trait locus mapping. In this study, bioinformatic prediction combined with PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution was examined, and for one RIP the impact on gene activity and phenotype was further evaluated. Results Five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, were identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was shown to act as an enhancer increasing the activities of TLR6 putative promoter and two mini-promoters. Furthermore, real-time quantitative polymerase chain reaction (qPCR) analysis revealed significant association (p < 0.05) of the ERV insertion with increased mRNA expression of TLR6, the neighboring gene TLR1, and genes downstream in the TLR signaling pathway such as MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) as well as the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in tissues of 30 day-old piglet. In addition, serum IL6 and TNFα concentrations were also significantly upregulated by the ERV insertion (p < 0.05). Conclusions A total of five RIPs were identified in five different TLR loci. The 192 bp ERV insertion in the first intron of TLR6 was associated with higher expression of TLR6, TLR1, and several genes downstream in the signaling cascade. Thus, the ERV insertion may act as an enhancer affecting regulation of the TLR signaling pathways, and can be potentially applied in breeding of disease resistant animals.

Download Full-text

An 192 bp ERV insertion in the first intron of TLR6 acts as an enhancer to increase TLR6 and TLR1 expression

10.21203/rs.3.rs-101173/v1 ◽

2020 ◽

Author(s):

xiaoyan wang ◽

Zixuan Chen ◽

Eduard Murani ◽

Enrico D'alessandro ◽

Yalong An ◽

...

Keyword(s):

Molecular Breeding ◽

Population Distribution ◽

Quantitative Polymerase Chain Reaction ◽

Adaptor Protein ◽

Small Gtpase ◽

Inflammatory Factors ◽

Neighboring Gene ◽

First Intron ◽

Disease Resistant ◽

Intron 1

Abstract Background Toll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR gene polymorphisms with diseases susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs) were developed recently as a new type of molecular marker having great potential in population genetics and quantitative trait locus (QTL) mapping analysis. In this study, bioinformatics prediction combined with the PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution and impact on gene activity and phenotype of one RIP was further evaluated. Results Totally, five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, were identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was proven to act as an enhancer increasing the activities of TLR6 promoter and multiple mini-promoters. Furthermore, the real-time quantitative polymerase chain reaction (qPCR) analysis demonstrated that the ERV insertion significantly enhances the mRNA expressions of TLR6, the neighboring gene TLR1, and the downstream genes MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1 ), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) of TLR signaling pathway and the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in 30-day piglet tissues. In addition, the serum IL-6 and TNFα were also significantly upregulated by ERV insertion. Conclusions Overall, five RIPs were identified in several TLRs, and the 192 bp ERV insertion in the first intron of TLR6 can improve the expressions of TLR6, TLR1, their downstream genes, and the inflammatory factors by acting as an enhancer affecting the regulation of TLR pathways, which may be applicable in the molecular breeding of disease resistant animals.

Download Full-text

An 192 bp ERV Insertion in the First Intron of TLR6 Acts as an Enhancer to Increase TLR6 and TLR1 Expression

10.21203/rs.3.rs-105672/v1 ◽

2020 ◽

Author(s):

xiaoyan wang ◽

Zixuan Chen ◽

Eduard Murani ◽

Enrico D'alessandro ◽

Yalong An ◽

...

Keyword(s):

Molecular Breeding ◽

Population Distribution ◽

Quantitative Polymerase Chain Reaction ◽

Adaptor Protein ◽

Small Gtpase ◽

Inflammatory Factors ◽

Neighboring Gene ◽

First Intron ◽

Disease Resistant ◽

Intron 1

Abstract BackgroundToll-like receptors (TLRs) play important roles in building innate immune and inducing adaptive immune responses. Associations of the TLR gene polymorphisms with diseases susceptibility, which are the basis of molecular breeding for disease resistant animals, have been reported extensively. Retrotransposon insertion polymorphisms (RIPs) were developed recently as a new type of molecular marker having great potential in population genetics and quantitative trait locus (QTL) mapping analysis. In this study, bioinformatics prediction combined with the PCR-based amplification was employed to screen for RIPs in porcine TLR genes. Their population distribution and impact on gene activity and phenotype of one RIP was been further evaluated. ResultsThe results showed that five RIPs, located at the 3' flank of TLR3, 5' flank of TLR5, intron 1 of TLR6, intron 1 of TLR7, and 3' flank of TLR8 respectively, was identified. These RIPs were detected in different breeds with an uneven distribution among them. By using the dual luciferase activity assay a 192 bp endogenous retrovirus (ERV) in the intron 1 of TLR6 was proven to act as an enhancer increasing the activities of TLR6 promoter and multiple mini-promoters. Furthermore, the real-time quantitative polymerase chain reaction (qPCR) analysis demonstrated that the ERV insertion significantly enhances the mRNA expressions of TLR6, the neighboring gene TLR1, and the downstream genes MyD88 (Myeloid differentiation factor 88), Rac1 (Rac family small GTPase 1), TIRAP (TIR domain containing adaptor protein), Tollip (Toll interacting protein) of TLR signaling pathway and the inflammatory factors IL6 (Interleukin 6), IL8 (Interleukin 8), and TNFα (Tumor necrosis factor alpha) in 30-day piglet tissues. In addition, the serum IL-6 and TNFα was also significantly upregulated by ERV insertion. ConclusionsOverall, five RIPs were been identified in several TLRs, and the 192 bp ERV insertion in the first intron of TLR6 can improve the expressions of TLR6, TLR1, their downstream genes, and the inflammatory factors by acting as an enhancer affecting the regulation of TLR pathways, which may be applicable in the molecular breeding of disease resistant animals.

Download Full-text

Autocrine Activity of Exosomes in Glucocorticoid-Induced Injury of Bone Microvascular Endothelial Cells Identified by Protein Array

10.21203/rs.3.rs-1070782/v1 ◽

2021 ◽

Author(s):

Qingyu Zhang ◽

Tengqi Li ◽

Zirong Li ◽

Jike Lu ◽

Xinjie Wu ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Transforming Growth Factor ◽

Quantitative Polymerase Chain Reaction ◽

Protein Array ◽

Inflammatory Factors ◽

Microvascular Endothelial Cells ◽

Total Protein Content ◽

Microvascular Endothelial ◽

The Impact

Abstract Background: Glucocorticoid could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head and the application of icariin showed a protective effect. However, the impact of autocrine exosomes during these processes is still to be confirmed.Methods: Exosomes were extracted from BMECs treated with hydrocortisone or hydrocortisone plus icariin by super-speed centrifugation; exosome-carried proteins were evaluated via BCA assay, Western blotting, protein array assay and Elisa test, while miRNA expression profile was assessed via high-throughput sequencing and confirmed by quantitative polymerase chain reaction (qPCR) to screen candidate molecules responsible for BMEC-Exo function. BMECs were incubated with and without exosomes before glucocorticoid intervention and then the impact of BMECs-derived exosomes on BMECs viability, apoptosis, migration, angiogenesis, and protein expression was further assessed by a series of functional assays. Results: Exosomes secreted by BMECs could ameliorate glucocorticoid-induced endothelial cellular injury, improve cell viability, decrease cell apoptosis, and promote cell migration and angiogenesis compared with the blank control. These effects of secreted exosomes could be reinforced by icariin intervention. Meanwhile, mechanism studies showed that expression level of eNOS, COX-2, and pERK were significantly increased while the cleaved caspase-3 level was decreased in BMECs after coculture with exosomes. Although icariin treatment would not significantly change the size and total protein content of BMECs-derived exosomes, expression of exosome-carried vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) was enhanced and numerous miRNAs involved in cell proliferation and apoptosis were up-regulated (e.g., hsa-miR-1469 and hsa-miR-133a-5p) or down-regulated (e.g., hsa-miR-10b-5p) (p < 0.05). 29 differentially expressed inflammatory factors were detected between the exosomes secreted by the Icariin-treated and the Model groups.Conclusion: To sum up, the present study indicates that autocrine exosomes could significantly improve glucocorticoid-induced injury of BMECs, partially mediated by activation of MAPK/ERK pathway and regulation of several inflammation/apoptosis/proliferation-associated proteins. Icariin intervention could reinforce these effects and may act as a promising drug for improving glucocorticoid-induced injury of BMECs. In vivo or animal studies are still required to better understand the function of BMEC-derived exosomes.

Download Full-text

Estimating epidemiologic dynamics from cross-sectional viral load distributions

Science ◽

10.1126/science.abh0635 ◽

2021 ◽

pp. eabh0635

Author(s):

James A. Hay ◽

Lee Kennedy-Shaffer ◽

Sanjat Kanjilal ◽

Niall J. Lennon ◽

Stacey B. Gabriel ◽

...

Keyword(s):

Population Distribution ◽

Quantitative Polymerase Chain Reaction ◽

Cross Sectional ◽

Outbreak Management ◽

Viral Loads ◽

Time Estimates ◽

Load Distributions ◽

Random Samples ◽

Combining Data ◽

Polymerase Chain

Estimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but case data used for such estimation are confounded by variable testing practices. We show that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values obtained from reverse-transcription quantitative polymerase chain reaction testing, changes during an epidemic. Thus, Ct values from even limited numbers of random samples can provide improved estimates of an epidemic’s trajectory. Combining data from multiple such samples improves the precision and robustness of such estimation. We apply our methods to Ct values from surveillance conducted during the SARS-CoV-2 pandemic in a variety of settings and offer alternative approaches for real-time estimates of epidemic trajectories for outbreak management and response.

Download Full-text

LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs

Open Medicine ◽

10.1515/med-2021-0200 ◽

2021 ◽

Vol 16 (1) ◽

pp. 117-127

Author(s):

Hongmei Gao ◽

Zhaohui Guo

Keyword(s):

Smooth Muscle ◽

Muscle Protein ◽

Umbilical Vein ◽

Smooth Muscle Actin ◽

Quantitative Polymerase Chain Reaction ◽

Density Lipoprotein ◽

Inflammatory Factors ◽

Luciferase Reporter ◽

Western Blot Assay ◽

Lactate Dehydrogenase Activity

Abstract Long noncoding RNAs (lncRNAs) have been verified as vital regulators in human disease, including atherosclerosis. However, the precise role of X-inactive-specific transcript (XIST) in atherosclerosis remains unclear. The proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to low-density lipoprotein (ox-LDL) were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide, and flow cytometry assays, correspondingly. The western blot assay was used to quantify protein expression. Lactate dehydrogenase activity and the concentrations of inflammatory factors were measured by matched kits. The real-time quantitative polymerase chain reaction (qPCR) was used to determine α-smooth muscle actin, smooth muscle protein 22-α, XIST, miR-98-5p, and pregnancy-associated plasma protein A (PAPPA) levels in HUVECs. The relationship among XIST, miR-98-5p, and PAPPA was analyzed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. We found ox-LDL repressed proliferation and induced inflammation and apoptosis in HUVECs. Loss-of-functional experiment suggested that the downregulation of XIST overturned the ox-LDL-induced effects on HUVECs. Additionally, overexpression of miR-98-5p-induced effects on ox-LDL-stimulated HUVECs was abolished by upregulation of XIST. However, silencing of miR-98-5p strengthened the ox-LDL-induced effects on HUVECs by increasing expression of PAPPA. Mechanistically, XIST could regulate PAPPA expression in ox-LDL-induced HUVECs by sponging miR-98-5p, providing understanding for atherosclerosis.

Download Full-text

The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05224-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Saeedeh Talebi ◽

Mahammad Safarian ◽

Mahmood Reza Jaafari ◽

Seyed Javad Sayedi ◽

Zahra Abbasi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Controlled Trial ◽

Genetic Disorder ◽

The Body ◽

Inflammatory Factors ◽

Secondary Outcome ◽

Nasopharyngeal Swab ◽

Nutritional Strategy ◽

Cftr Protein ◽

The Impact

Abstract Background Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. Methods This prospective, double blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. Discussion Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. Trial registration Iranian Registry of Clinical Trials IRCT20200705048018N1. Registered on July 10, 2020.

Download Full-text

Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation

Journal of Neuroinflammation ◽

10.1186/s12974-019-1644-8 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 8

Author(s):

Xiaoxia Ye ◽

Mingming Zhu ◽

Xiaohang Che ◽

Huiyang Wang ◽

Xing-Jie Liang ◽

...

Keyword(s):

Inflammatory Response ◽

Microglial Activation ◽

Adaptor Protein ◽

Mtor Pathway ◽

Microglial Cells ◽

Inflammatory Factors ◽

Intraventricular Injection ◽

Enzyme Linked Immunosorbent Assay ◽

Autophagic Flux

Abstract Background Microglial activation is a prominent feature of neuroinflammation, which is present in almost all neurodegenerative diseases. While an initial inflammatory response mediated by microglia is considered to be protective, excessive pro-inflammatory response of microglia contributes to the pathogenesis of neurodegeneration. Although autophagy is involved in the suppression of inflammation, its role and mechanism in microglia are unclear. Methods In the present study, we studied the mechanism by which lipopolysaccharide (LPS) affects microglial autophagy and the effects of autophagy on the production of pro-inflammatory factors in microglial cells by western blotting, immunocytochemistry, transfection, transmission electron microscopy (TEM), and real-time PCR. In a mouse model of neuroinflammation, generated by intraventricular injection of LPS (5 μg/animal), we induced autophagy by rapamycin injection and investigated the effects of enhanced autophagy on microglial activation by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Results We found that autophagic flux was suppressed in LPS-stimulated N9 microglial cells, as evidenced by decreased expression of the autophagy marker LC3-II (lipidated form of MAP1LC3), as well as increased levels of the autophagy adaptor protein SQSTM1. LPS significantly decreased Vps34 expression in N9 microglial cells by activating the PI3KI/AKT/MTOR pathway without affecting the levels of lysosome-associated proteins and enzymes. More importantly, overexpression of Vps34 significantly enhanced the autophagic flux and decreased the accumulation of SQSTM1 in LPS-stimulated N9 microglial cells. Moreover, our results revealed that an LPS-induced reduction in the level of Vps34 prevented the maturation of omegasomes to phagophores. Furthermore, LPS-induced neuroinflammation was significantly ameliorated by treatment with the autophagy inducer rapamycin both in vitro and in vivo. Conclusions These data reveal that LPS-induced neuroinflammation in N9 microglial cells is associated with the inhibition of autophagic flux through the activation of the PI3KI/AKT/MTOR pathway, while enhanced microglial autophagy downregulates LPS-induced neuroinflammation. Thus, this study suggests that promoting the early stages of autophagy might be a potential therapeutic approach for neuroinflammation-associated diseases.

Download Full-text

The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity

Cancers ◽

10.3390/cancers13112574 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2574

Author(s):

Jee Soo Park ◽

Myung Eun Lee ◽

Won Sik Jang ◽

Koon Ho Rha ◽

Seung Hwan Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Quantitative Polymerase Chain Reaction ◽

Parp Inhibitor ◽

Renal Tumors ◽

Low Grade ◽

Normal Kidney ◽

The Dead ◽

The Impact

Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.

Download Full-text

Sequence requirements for premature transcription arrest within the first intron of the mouse c-fos gene

Molecular and Cellular Biology ◽

10.1128/mcb.11.5.2832-2841.1991 ◽

1991 ◽

Vol 11 (5) ◽

pp. 2832-2841

Author(s):

N Mechti ◽

M Piechaczyk ◽

J M Blanchard ◽

P Jeanteur ◽

B Lebleu

Keyword(s):

Rna Polymerase Ii ◽

In Vitro Transcription ◽

Rna Transcripts ◽

First Intron ◽

Nuclear Extracts ◽

Intron 1 ◽

A Cell ◽

Sequence Requirements

A strong block to the elongation of nascent RNA transcripts by RNA polymerase II occurs in the 5' part of the mammalian c-fos proto-oncogene. In addition to the control of initiation, this mechanism contributes to transcriptional regulation of the gene. In vitro transcription experiments using nuclear extracts and purified transcription templates allowed us to map a unique arrest site within the mouse first intron 385 nucleotides downstream from the promoter. This position is in keeping with that estimated from nuclear run-on assays performed with short DNA probes and thus suggests that it corresponds to the actual block in vivo. Moreover, we have shown that neither the c-fos promoter nor upstream sequences are absolute requirements for an efficient transcription arrest both in vivo and in vitro. Finally, we have characterized a 103-nucleotide-long intron 1 motif comprising the arrest site and sufficient for obtaining the block in a cell-free transcription assay.

Download Full-text

Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00370.2020 ◽

2021 ◽

Author(s):

Tetsuo Takehara ◽

Naoki Mizutani ◽

Hayato Hikita ◽

Yoshinobu Saito ◽

Yuta Myojin ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Injury ◽

Cell Viability ◽

Liver Regeneration ◽

Adaptor Protein ◽

Chronic Liver ◽

Hepatocyte Apoptosis ◽

Chronic Liver Injury ◽

The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

Download Full-text