17 research outputs found
The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese
BACKGROUND: Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition. METHODS: In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls. RESULTS: The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10(-5), odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects. CONCLUSION: HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN
B and T Lymphocyte Attenuator Down-regulation by HIV-1 Depends on Type I Interferon and Contributes to T-Cell Hyperactivation
Background. Nonspecific T-cell hyperactivation is the main driving force for human immunodeficiency virus (HIV)–1 disease progression, but the reasons why the excess immune response is not properly shut off are poorly defined
Cryotherapy is Associated with Improved Clinical Outcomes of Sorafenib Therapy for Advanced Hepatocellular Carcinoma
FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells
Abstract Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility
Systematic Analysis of the Lysine Succinylome in Candida albicans
Candida albicans is the most common human fungal
pathogen for both immunocompetent and immunocompromised individuals.
Lysine succinylation is a frequently occurring post-translational
modification that is found in many organisms; however, the role of
succinylation is still under investigation. Here, we initiated a first
screening of lysine succinylation in C. albicans. We identified 1550 succinylation sites from 389 proteins in C. albicans, demonstrating that succinylation is
conservative in this organism. However, the lysine succinylation sites
showed some difference in C. albicans, with the overlapping rates between C. albicans and other species ranging from 55% for Saccharomyces
cerevisiae, 40% for human, 35% for mouse, and to only
16% for Escherichia coli. The further
bioinformatics analysis indicated that the succinylated proteins were
involved in a wide range of cellular functions with diverse subcellular
localizations. Furthermore, we discovered that lysine succinylation
could coexist with phosphorylation and/or acetylation in C. albicans. The KEGG enrichment pathway analysis
of these succinylated proteins suggested that succinylation may play
an indispensable role in the regulation of the tricarboxylic acid
cycle. The bioinformatic data obtained from this study therefore enable
the depth-resolved physiological roles of lysine succinylation in C. albicans
Systematic Analysis of the Lysine Succinylome in Candida albicans
Candida albicans is the most common human fungal
pathogen for both immunocompetent and immunocompromised individuals.
Lysine succinylation is a frequently occurring post-translational
modification that is found in many organisms; however, the role of
succinylation is still under investigation. Here, we initiated a first
screening of lysine succinylation in C. albicans. We identified 1550 succinylation sites from 389 proteins in C. albicans, demonstrating that succinylation is
conservative in this organism. However, the lysine succinylation sites
showed some difference in C. albicans, with the overlapping rates between C. albicans and other species ranging from 55% for Saccharomyces
cerevisiae, 40% for human, 35% for mouse, and to only
16% for Escherichia coli. The further
bioinformatics analysis indicated that the succinylated proteins were
involved in a wide range of cellular functions with diverse subcellular
localizations. Furthermore, we discovered that lysine succinylation
could coexist with phosphorylation and/or acetylation in C. albicans. The KEGG enrichment pathway analysis
of these succinylated proteins suggested that succinylation may play
an indispensable role in the regulation of the tricarboxylic acid
cycle. The bioinformatic data obtained from this study therefore enable
the depth-resolved physiological roles of lysine succinylation in C. albicans