Signal Transducer And Activator Of Transcription 5A Research Articles

Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway

PurposeTo explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying.Methods and resultsTCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer.ConclusionThe present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

MiR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells.

αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

Extremely low-frequency electromagnetic field (ELF-EMF) induces alterations in epigenetic regulation in the myometrium – An in vitro study

Previous research by the authors indicated that an extremely low-frequency electromagnetic field (ELF-EMF) evokes molecular alterations in the porcine myometrium. It was hypothesized that the ELF-EMF could induce alterations in the epigenetic regulation of gene expression in the myometrium. In the current study, slices of the porcine myometrium during the peri-implantation period (n = 4) were used for further in vitro exposition to ELF-EMF (50 Hz, 8 mT, 2 h treatment duration). The study tested whether the ELF-EMF may affect: 1/the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and DNA (cytosine-5)-methyltransferase 3a (DNMT3a), 2/the level of genomic DNA methylation, and 3/the level of amplification of methylated and unmethylated variants of promoter regions of selected genes with altered expression in response to ELF-EMF. It was found that ELF-EMF treatment increased DNMT1, decreased DNMT3a mRNA transcript and protein abundance, and increased the level of genomic DNA methylation. The direction of alterations in the level of amplification of methylated and unmethylated variants of the promoter region of selected genes with altered expression, i.e. prodynorphin (PDYN), interleukin 15 (IL15) signal transducer and activator of transcription 5A (STAT5A), tumor necrosis factor (TNF), and between down-regulated genes were early growth response 2 (EGR2), hyaluronan and proteoglycan link protein 1 (HAPLN1), and uteroferrin associated basic protein-2 (UABP2), mostly involving the direction of changes in their transcriptional activity, which was evaluated in a previous study by the authors. Thus, ELF-EMF radiation disturbs epigenetic mechanisms, which may underlay ELF-EMF-related transcriptomic alterations in the myometrium.

Prolactin regulates RANKL expression via signal transducer and activator of transcription 5a signaling in mammary epithelial cells of dairy cows.

Receptor of activated nuclear factor kappa B ligand (RANKL) is regulated by prolactin in the mammary gland. However, the intrinsic molecular mechanism is not well understood. Herein, mammary epithelial cells (MECs) of dairy cows were isolated to characterize the molecular mechanism of prolactin in vitro. We demonstrated that prolactin stimulation increased the expression of RANKL in MECs. Moreover, the expression of RANKL induced by prolactin was inhibited by the prolactin receptor or signal transducer and activator of transcription 5A (STAT5a) knockdown. Furthermore, prolactin markedly increased RANKL-Luciferase reporter activity in MECs. We identified a putative gamma-interferon activated site (GAS) in the region between residues -883 to -239 bp of the RANKL promoter. Subsequently, we found that the mutated GAS sequence failed to respond to prolactin stimulation. In addition, STAT5a knockdown markedly decreased prolactin-stimulated RANKL promoter activity. Western blot results revealed that RANKL overexpression markedly decreased the STAT5a phosphorylation level in MECs. These findings indicate that prolactin could regulate RANKL promoter activity via STAT5a, contributing to increased RANKL expression in MECs. RANKL may have a negative regulatory effect on STAT5a activity.

The Kruppel-like factor 4-signal transducer and activator of transcription 5A axis promotes pancreatic fibrosis in mice with caerulein-induced chronic pancreatitis.

Pancreatic fibrosis (PF) is a hallmark of chronic pancreatitis (CP), but its molecular mechanism remains unclear. This study was conducted to explore the role of Kruppel-like factor 4 (KLF4) in PF in CP mice. The CP mouse model was established using caerulein. After KLF4 interference, pathological changes in pancreatic tissues and fibrosis degree were observed by hematoxylin-eosin staining and Masson staining, and levels of Collagen I, Collagen III, and alpha-smooth muscle actin, inflammatory cytokines, KLF4, signal transducer and activator of transcription 5A (STAT5) in pancreatic tissues were measured by enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blot assay, and immunofluorescence. The enrichment of KLF4 on the STAT5 promoter and the binding of KLF4 to the STAT5 promoter were analyzed. The rescue experiments were performed by co-injection of sh-STAT5 and sh-KLF4 to confirm the regulatory mechanism of KLF4. KLF4 was upregulated in CP mice. Inhibition of KLF4 effectively attenuated pancreatic inflammation and PF in mice. KLF4 was enriched on the STAT5 promoter and enhanced the transcriptional and protein levels of STAT5. Overexpression of STAT5 reversed the inhibitory role of silencing KLF4 in PF. In summary, KLF4 promoted the transcription and expression of STAT5, which further facilitated PF in CP mice.

Ubiquitous toxicity of Mercuric Chloride in target tissues and organs: Impact of Ubidecarenone and liposomal-Ubidecarenone STAT 5A/ PTEN /PI3K/AKT signaling pathways

BackgroundMercuric chloride (HgCl3) is categorized as class II B hazardous metal that is present in many occupational and environmental conditions. In the meantime, Hg exists in the environment in such an abundant manner, it is virtually impossible for humans to avoid exposure to different forms of Hg. In addition to environmental exposure, individuals may be exposed to Hg from dental amalgams, medicinal treatments and dietary sources. Nevertheless, Liposomal drug delivery system is a promising era in the field of Nano-medicine and have the advantageous of increasing drug bioavailability and retention phenomena in addition to targeting organ for all mentioned the present study was designed to investigate the hypothesis that messenger RNA gene expression of Signal transducer and activator of transcription- 5 A (STAT-5A), Phosphatase and tensin homolog (PTEN), phosphoinositol kinase (PI3K) and alpha serine/threonine-protein kinase (AKT) can trigger HgCl3 induced nephrotoxicity post Ubidecarenone and liposomal Ubidecarenone therapy. MethodsHgCl3 toxicity was induced in rats via a dose of 5 mg/kg BW for one week followed by Ubidecarenone and liposomal Ubidecarenone therapy in a dose of 10 & 3 mg/kg BW for one month, respectively. Then kidney function tests, Glutathione and gene expression for PI3K, AKT, PTEN and STAT-5A was investigated. ResultsHgCl3 intoxication significantly up regulated PI3K, AKT, PTEN and STAT-5A signaling pathways meanwhile, Ubidecarenone and liposomal- Ubidecarenone treatment significantly reduced PI3K, AKT, PTEN and STAT-5A gene expression post HgCl3 intoxication with the liposomal regimen revealing the most significant impact. Furthermore, renal toxicity was confirmed via monitoring urea and creatinine which were modulated post Ubidecarenone and liposomal-Ubidecarenone treatment. Wide evidence declared that mercuric S-conjugates of small endogenous thiols (such as Hcy, NAC and Cys) are probably the main transportable forms of Hg2+ to the kidneys thus reduced glutathione was investigated which reflected a significant down regulation post Hgcl3 toxicity. Conclusionliposomal drug delivery system including liposomal-Ubidecarenone can be considered as a prospective candidate for treating HgCl3 renal toxicity via modulating STAT-5A, PTEN, PI3K and AKT signaling pathways and via increasing retention time, bioavailability, shielding from macrophage recognition and targeting organs.

Polymorphism of the Signal Transducer and Activator of Transcription 5A (STAT5A) gene in Egyptian water buffaloes using the SSCP technique

Polymorphism of the Signal Transducer and Activator of Transcription 5A (STAT5A) gene in Egyptian water buffaloes using the SSCP technique

STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy.

Diabetic nephropathy (DN), one of microvascular complications of diabetes mellitus, results in renal dysfunction and end-stage renal disease. Recently, endothelial-to-mesenchymal transition (EndMT) was reported to mediate glomerular endothelial dysfunction, therefore, participating in the progress of fibrosis in DN. As a special type of epithelial-to-mesenchymal transition, EndMT and epithelial-to-mesenchymal transition may share corporate modulators. It was reported that epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1 (ELTD1) and signal transducer and activator of transcription 5A (STAT5A) participate in epithelial-to-mesenchymal transition in some situations. In this work, we proposed that STAT5A participated in high glucose-mediated EndMT via modulation of ELTD1 levels in DN. Our data indicated that hyperglycemia/high glucose-induced ELTD1 and EndMT in DN rats and hyperglycemic human glomerular endothelial cells (HGECs). Additionally, high glucose mediated STAT5A nuclear translocation in HGECs. High glucose-mediated EndMT was reversed by ELTD1 silencing. Moreover, STAT5A was found to be elevated in DN rats and hyperglycemic HGECs. The effect of high glucose-mediated increase of ELTD1 expression and EndMT was reversed by STAT5A silencing in vitro. Further, STAT5A overexpression enhanced ELTD1 levels and EndMT, which was inhibited by si-ELTD1. Chromatin immunoprecipitation (ChIP) and luciferase assay represented that STAT5A directly regulated ELTD1 transcription. Signal transducer and activator of transcription 5A directly regulated ELTD1 transcription, therefore, participating in high glucose-mediated EndMT in glomeruli of DN.

Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

STATs (Signal Transducers and Activators of Transcription) 5A and 5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH) and prolactin in fat cells. Previous studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. Male and female mice harboring adipocyte-specific deletion of both STAT5 genes (STAT5AKO) exhibit increased subcutaneous or inguinal adipose tissue mass, but no changes in visceral or gonadal fat mass. Both depots display substantial increases in adipocyte size with no changes in lipolysis in adipose tissue explants. RNA sequencing analysis of subcutaneous adipose tissue and indirect calorimetry experiments reveal sex-dependent differences in adipose gene expression and whole-body energy expenditure, respectively, resulting from the loss of adipocyte STAT5.

The long non-coding RNA T cell leukemia homeobox 1 neighbor enhances signal transducer and activator of transcription 5A phosphorylation to promote colon cancer cell invasion, migration, and metastasis

ABSTRACT Colon cancer is among the most prevalent gastrointestinal tumor types. The long noncoding RNA (lncRNA) T cell leukemia homeobox 1 neighbor (TLX1NB) is up-regulated in colorectal cancer (CRC). However, the functional role of this lncRNA in colon cancer remains unknown. In our study, we investigated the clinical significance of TLX1NB in colon cancer through bioinformatics analysis and explored its role in migration, invasion and metastasis of colon cancer cell with a series of experiments. Firstly, TLX1NB was up-regulated in colon cancer tissues and increased TLX1NB expression was significantly associated with advanced N stages. In wound healing assays and transwell assays, TLX1NB overexpression promoted HCT116 cell migration and invasion while TLX1NB knockdown inhibited SW620 cell migration and invasion. In vivo, TLX1NB knockdown suppressed pulmonary metastasis of SW620 cell and vimentin expression but increased E-cadherin expression. Then, TLX1NB overexpression enhanced signal transducer and activator of transcription 5A (STAT5A) phosphorylation and TLX1NB knockdown suppressed STAT5A phosphorylation. Moreover, the inhibition of STAT5A phosphorylation reversed TLX1NB overexpression-associated increase in HCT116 cell migratory and invasive activity. In conclusion, TLX1NB enhances STAT5A phosphorylation to promote colon cancer cell invasion, migration, and metastasis.

Polymorphism of bovine STAT5A gene and its association with milk production traits in crossbred cattle of Kerala, India

Signal transducer and activator of transcription 5A (STAT5A) is a transcription factor that mediates signals fromprolactin and growth hormone, the corresponding main regulators of lactation and growth of mammals. STAT5A issuggested to be candidate marker gene for quantitative traits in dairy cattle with respect to milk production traits. The objectives of present study were to investigate polymorphism of bovine STAT5A gene and its probable association with milk yield and milk-constituent traits in crossbred cattle. Crossbred cattle (250) in different farms of Kerala Veterinary and Animal Sciences University and different field centres of ICAR-Field progeny testing scheme,Thrissur were screened for polymorphism in exon-8 region of STAT5A gene using PCR-single-strand conformationpolymorphism analysis. A synonymous polymorphism (C/T) was found at position 1071 in exon 8. All three possiblegenotypes were identified with estimated frequencies of 0.584 (CC), 0.332 (CT) and 0.084 (TT); the estimated allelefrequencies were 0.75 (C) and 0.25 (T). The C/T genotypes demonstrated significant impact on milk fat per centbeing significantly higher in CC genotype cattle in comparison to other genotypes. It is evident by this investigationthat STAT5A polymorphism could be a promising indirect marker to improve milk production in crossbred cattle ofKerala.

STAT5A modulates CDYL2/SLC7A6 pathway to inhibit the proliferation and invasion of hepatocellular carcinoma by targeting to mTORC1.

Chromodomain Y-like 2 (CDYL2), as a member of CDY family known to be involved in spermatogenesis, has been reported to participate in breast cancer development recently, but its exact biological role in hepatocellular carcinoma (HCC) remains unclear. Here, we observed that CDYL2 was down-regulated in human primary HCC tissues and the low levels of CDYL2 expression were correlated with poor survival. Gain- and loss-of-function experiments showed that CDYL2 inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, CDYL2 down-regulates solute carrier family 7 member 6 (SLC7A6) by decreasing the enrichment of H3K4me3 on the promoter region of SLC7A6. Additionally, we also found that signal transducer and activator of transcription 5A (STAT5A) could directly and positively regulate the expression of CDYL2. Thus, CDYL2 was regulated by STAT5A, and suppressed the amino acid transportation through down-regulation of SLC7A6, and then inhibits the mTORC1/S6K pathway, a master regulator of cell growth. Consistently, CDYL2 expression correlated significantly with STAT5A and SLC7A6 expression in HCC. Collectively, we propose a model for a STAT5A/CDYL2/SLC7A6 axis that provides novel insight into CDYL2, which may serve as a potential factor for predicting prognosis and a therapeutic target for HCC patients.

Two Nipped-B-Like Protein A (Nipbla) Gametologs in Chinese Tongue Sole (Cynoglossus semilaevis): The Identification of Alternative Splicing, Expression Pattern, and Promoter Activity Analysis

In mammals, the mutation of nipped-B-like protein (nipbl) leads to Cornelia de Lange Syndrome (CdLS), characterized by low birth weight, short stature, and structural abnormalities of the skeleton, heart, and gut. In Chinese tongue sole (Cynoglossus semilaevis), a typical marine fish exhibiting sexual size dimorphism, the nipbl homolog gene (nipped-B-like protein A (nipbla)) was also screened with female higher expression level by somatotropic and reproductive tissues’ transcriptomic analysis. In this study, two nipbla genes, namely, nipbla-w and nipbla-z, were identified from the W and Z chromosomes of C. semilaevis, respectively. Similar to other mammalian and fish species nipbl, the two homolog proteins of C. semilaevis contained two conserved domains, namely, cohesion_HEAT and Nipped-B_C. The phylogenetic tree analysis showed that these two nipbla gametolog proteins were first clustered together and then grouped with other fish species. At least two types of alternative splicing sites were observed in exon 12 of the nipbla-z gene, which produced nipbla-z-tv1 and nipbla-z-tv2. Also, the sex-biased expression patterns of different nipbla-w and nipbla-z transcripts in female and male tissues were revealed by quantitative PCR (qPCR). The highest expression level of nipbla-w was observed in female gonad. While nipbla-z-tv1 exhibited relatively high expression in the muscle, liver, gonad, and brain, nipbla-z-tv2 only showed its expression superiority in the muscle of male individuals. The promoter regions of nipbla genes were amplified, and their transcription activity was successfully verified by a dual-luciferase reporter system. After nipbla-w and nipbla-z knockdown in the brain cell lines by RNA interference, a series of growth-related genes were influenced, including Bone Morphogenetic Protein 4 (bmp4), Wnt Family Member 11 (wnt11), and Sprouty Related EVH1 Domain Containing 2 (spred2). The prediction of transcription factors suggested that c-Jun, sex-determining region Y (SRY), POU Class 1 Homeobox 1 (POU1F1a), myogenic differentiation antigen (MyoD), signal transducer and activator of transcription 5a (STAT5A), and nuclear factor I C (Nfic) might be the putative upstream regulatory factors for nipbla; among them, c-Jun has been verified to effectively regulate the transcriptional activity of nipbla. The identification of two nipbla genes provided important data for interpreting the sexual size dimorphism in C. semilaevis.

Single nucleotide polymorphism in STAT5A could not endorse variation in milk production traits in Indian bovine population.

The Signal Transducer and Activator of Transcription 5A (STAT5A) gene involved in activating the transcription of milk protein genes was predicted to be influencing milk production traits. The present study was undertaken to investigate the suitability of the polymorphism of STAT5A as a marker for milk traits in Ongole, crossbred cattle and Murrah buffaloes from Southern India. Blood samples (n = 502) for DNA isolation and milk samples (n = 222) from different genetic groups were collected from various farms. The gene variants upon polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on the exon 7 region of STAT5A were subjected to GLM analysis to evaluate their association with milk production traits. The frequencies of C and T alleles at the STAT5A/AvaI locus were 0.98 and 0.02 (Jersey crossbred), 0.94 and 0.06 [Holstein-Friesian (HF) crossbred], 0.97 and 0.03 (Ongole). T allele was not observed in Murrah buffaloes. The least squares mean lactation milk yield of CC and CT genotypes of STAT5A were 2,096.90 ± 48.63 and 2,294.41 ± 215.85 kg in Jersey crossbred, 2,312.92 ± 91.01 and 2,392.82 ± 207.66 kg in HF crossbred and 528.40 ± 22.10 and 396.37 ± 76.17 kg in Ongole cattle, respectively. The milk fat content of the CC genotype was higher (P > 0.05) in Jersey crossbred cattle. The CT genotypes of Ongole and HF crossbred cattle recorded a higher fat per cent than the CC genotypes. Significant associations were not observed in support of STAT5A as a marker for milk production traits in either Ongole or crossbred cattle of indicine admixture and no reason could be found to consider this locus as universal markers for milk production traits in indicine cattle and buffaloes. Considering the monomorphic nature of the gene in buffaloes and their higher milk fat content as compared to bovine milk, much remains to be explored regarding the underlying differences across the bovine and the bubaline species.

Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription.

Inhibitors of histone deacetylases (HDACi) have shown promising effects in preclinical applications for the treatment of many diseases. Confusedly though, the effects of the HDACi trichostatin A (TSA) on angiogenesis are variable among different diseases. This study investigated the direct effects of TSA on endothelial cells, which plays essential roles in angiogenesis and the underlying molecular events. TSA reduced the viability of human umbilical vein endothelial cells (HUVECs), in which proliferation-related genes including BIRC5, CKS1B, and NDC80 were found to be involved. Furthermore, signal transducer and activator of transcription 5 A (STAT5A) was demonstrated to be reduced by TSA and to mediate TSA-induced downregulation of BIRC5, CKS1B, and NDC80 and HUVEC proliferation. Mechanistically, data showed that STAT5A directly bound to the promoters of BIRC5, CKS1B, and NDC80 and activated their transcription through special DNA sequence sites. Finally, the TSA–STAT5A–BIRC5, CKS1B, and NDC80 axis also worked in a cancerous endothelial cell angiogenesis model. The results of this study revealed novel mechanisms underlying the effects of TSA on endothelial cells and provided insights for angiogenesis-associated diseases.

A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

AbstractThe transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

MiR-204-5p and miR-211 Synergistically Downregulate the αS1-Casein Content and Contribute to the Lower Allergy of Goat Milk.

αS1-Casein (encoded by the CSN1S1 gene) is associated with higher rates of allergy than other milk protein components for humans. microRNAs (miRNAs) as small noncoding RNA molecules regulate gene expression and influence diverse biological processes. However, little is known about the regulation of milk protein synthesis by miRNAs in ruminants. In this study, we aim to investigate the regulatory roles of miR-204 family members (miR-204-5p and miR-211) on αS1-casein in goat mammary epithelial cells (GMEC). Here, we observed that the CSN1S1 mRNA level is upregulated, while miR-204-5p and miR-211 (miR-204-5p/-211) abundance is downregulated during peak lactation compared with middle lactation of dairy goats. We found that miR-204-5p/-211 synergistically inhibit αS1-casein expression via directly binding to the 3'-untranslated region (3'UTR) of CSN1S1 in GMEC. miR-204-5p/-211 increase β-casein mRNA (CSN2) and protein abundance, as well as the signal transducer and activator of transcription 5a (STAT5a) activity. Further, miR-204-5p/-211 enhance β-casein expression via the CSN1S1-STAT5a signaling axis and promote β-casein transcription by activating the STAT5 response element located in the CSN2 promoter. In conclusion, miR-204-5p/-211 regulate αS1-casein and β-casein synthesis via targeting CSN1S1 in GMEC, which provide the strategy for manipulating miR-204 family members to reduce milk allergy potential and improve ruminant milk quality for human consumption.

Detection of the potentiality before the actuality: Measurement of T-cell proliferation before cell division occurs.

Detection of the potentiality before the actuality: Measurement of T-cell proliferation before cell division occurs.

Protein regulation strategies of the mouse spleen in response to Babesia microti infection

BackgroundBabesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured but still actively initiates immunomodulatory responses.MethodsTo explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and in phosphorylation modification in spleen tissue after Babesia microti infection in mice.ResultsAfter mice were infected with B. microti, their spleens were seriously damaged. Using bioinformatics methods to analyse dynamic changes in a large number of proteins, we found that the spleen still initiated immune responses to combat the infection, with immune-related proteins playing an important role, including cathepsin D (CTSD), interferon-induced protein 44 (IFI44), interleukin-2 enhancer-binding factor 2 (ILF2), interleukin enhancer-binding factor 3 (ILF3) and signal transducer and activator of transcription 5A (STAT5A). In addition, some proteins related to iron metabolism were also involved in the repair of the spleen after B. microti infection, including serotransferrin, lactoferrin, transferrin receptor protein 1 (TfR1) and glutamate-cysteine ligase (GCL). At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including protein kinase C-δ (PKC-δ), mitogen-activated protein kinase (MAPK) 3/1, growth factor receptor-bound protein 2 (Grb2) and P21-activated kinase 2 (PAK2).ConclusionsImmune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important role in the regulation of spleen injury and maintenance of homeostasis. This study provides an important basis for the diagnosis and treatment of babesiosis.Graphical

Evolutionary Divergence of Signal Transducer and Activator of Transcription 5A (STAT5A) Gene in Riverine Buffalo

Evolutionary Divergence of Signal Transducer and Activator of Transcription 5A (STAT5A) Gene in Riverine Buffalo