Role of the JAK-STAT Pathway in Bovine Mastitis and Milk Production

Khan, Muhammad Zahoor; Khan, Adnan; Xiao, Jianxin; Ma, Yulin; Ma, Jiaze; Gao, Jian; Cao, Zhijun

doi:10.3390/ani10112107

Cited by 42 publications

(29 citation statements)

References 131 publications

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“…SOCS2 inhibits the GH/IGF-1 axis and negatively regulates growth and development after birth [ 60 , 61 ], whereas SOCS3 inhibits the EPO signaling pathways [ 62 ]. Moreover, previous studies report a close association between the signaling pathways and the lactation regulatory factors [ 63 , 64 ]. This study analyzed the expression and protein levels of SOCS2 and SOCS3 genes to decipher their involvement in the expression of milk protein and fat synthesis-related factors.…”

Section: Discussionmentioning

confidence: 99%

Beta-Sitosterol Promotes Milk Protein and Fat Syntheses-Related Genes in Bovine Mammary Epithelial Cells

Liu

Shen

Zong

et al. 2021

Animals

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β-sitosterol, a phytosterol with multiple biological activities, has been used in the pharmaceutical industry. However, there are only a few reports on the use of β-sitosterol in improving milk synthesis in dairy cows. This study aimed to investigate the effects of β-sitosterol on milk fat and protein syntheses in bovine mammary epithelial cells (MAC-T) and its regulatory mechanism. MAC-T cells were treated with different concentrations (0.01, 0.1, 1, 5, 10, 20, 30, or 40 μM) of β-sitosterol, and the expression levels of milk protein and fat synthesis-related genes and proteins were analyzed. β-sitosterol at 0.1, 1, and 10 μM concentrations promoted the mRNA and protein expression of β-casein. β-sitosterol (0.1, 1, 10 μM) increased the mRNA and protein expression levels of signal transducer activator of transcription 5 (STAT5), mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase beta-1 (S6K1) of the JAK2/STAT5 and mTOR signaling pathways. It also stimulated the milk fat synthesis-related factors, including sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor-gamma (PPARγ), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), and stearyl CoA desaturase (SCD). β-sitosterol (0.1, 1, 10 μM) also significantly increased the expression of growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and hypoxia-inducible factor-1α (HIF-1α)-related genes. Notably, the compound inhibited the expression of the negative regulator, the suppressor of cytokine signaling 2 (SOCS2) at the two lower concentrations (0.1, 1 μM), but significantly promoted the expression at the highest concentration (30 μM). These results highlight the role of β-sitosterol at concentrations ranging from 0.1 to 10 μM in improving milk protein and fat syntheses, regulating milk quality. Therefore, β-sitosterol can be used as a potential feed additive to improve milk quality in dairy cows.

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Section: Discussionmentioning

confidence: 99%

Beta-Sitosterol Promotes Milk Protein and Fat Syntheses-Related Genes in Bovine Mammary Epithelial Cells

Liu

Shen

Zong

et al. 2021

Animals

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“…Furthermore, Zhao et al (58) found that lncRNA UCA1 could accelerate cell viability, block apoptosis and function as competitive endogenous RNA (ceRNA) to target TLR4 by sponging miR-499b-5p, thereby alleviating the LPS-challenged cell damage. Based on above results, it was speculated that these DElncRNAs are likely involved in regulating the process of bovine mastitis via their immune-related target genes (7,(59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 97%

Differential Expression Profiles of lncRNA Following LPS-Induced Inflammation in Bovine Mammary Epithelial Cells

Wang

Yang

et al. 2021

Front. Vet. Sci.

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Bovine mastitis is an inflammatory response of mammary glands caused by pathogenic microorganisms such as Escherichia coli (E. coli). As a key virulence factor of E. coli, lipopolysaccharide (LPS) triggers innate immune responses via activation of the toll-like-receptor 4 (TLR4) signaling pathway. However, the molecular regulatory network of LPS-induced bovine mastitis has yet to be fully mapped. In this study, bovine mammary epithelial cell lines MAC-T were exposed to LPS for 0, 6 and 12 h to assess the expression profiles of long non-coding RNAs (lncRNAs) using RNA-seq. Differentially expressed lncRNAs (DElncRNAs) were filtered out of the raw data for subsequent analyses. A total of 2,257 lncRNAs, including 210 annotated and 2047 novel lncRNAs were detected in all samples. A large proportion of lncRNAs were present in a high abundance, and 112 DElncRNAs were screened out at different time points. Compared with 0 h, there were 22 up- and 25 down-regulated lncRNAs in the 6 h of post-infection (hpi) group, and 27 up- and 22 down-regulated lncRNAs in the 12 hpi group. Compared with the 6 hpi group, 32 lncRNAs were up-regulated and 25 lncRNAs were down-regulated in the 12 hpi group. These DElncRNAs are involved in the regulation of a variety of immune-related processes including inflammatory responses bMECs exposed to LPS. Furthermore, lncRNA TCONS_00039271 and TCONS_00139850 were respectively significance down- and up-regulated, and their target genes involve in regulating inflammation-related signaling pathways (i.e.,Notch, NF-κB, MAPK, PI3K-Akt and mTOR signaling pathway), thereby regulating the occurrence and development of E. coli mastitis. This study provides a resource for lncRNA research on the molecular regulation of bovine mastitis

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“…Key proteins in the cAMP, PI3K-Akt, Prolactin, and Ras pathways and PPI networks obtained from KEGG pathway enrichment analysis interact with each other to form a complex target−pathway network. For example, the downstream proteins of the Prolactin pathway are JAK2, MAPK, and SRC and regulate apoptosis and inflammation through the JAK/STAT pathway [61][62][63]. MAPK integrates crosstalk with multiple signaling pathways, such as the Ras/MAPK pathway, ErbB pathway, and PI3K-Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

Dong

Liu

Zou

et al. 2021

Veterinary Sciences

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Based on network pharmacological analysis and molecular docking techniques, the main components of M. cordata for the treatment of bovine relevant active compounds in M. cordata were searched for through previous research bases and literature databases, and then screened to identify candidate compounds based on physicochemical properties, pharmacokinetic parameters, bioavailability, and drug-like criteria. Target genes associated with hoof disease were obtained from the GeneCards database. Compound−target, compound−target−pathway−disease visualization networks, and protein−protein interaction (PPI) networks were constructed by Cytoscape. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in R language. Molecular docking analysis was done using AutoDockTools. The visual network analysis showed that four active compounds, sanguinarine, chelerythrine, allocryptopine and protopine, were associated with the 10 target genes/proteins (SRC, MAPK3, MTOR, ESR1, PIK3CA, BCL2L1, JAK2, GSK3B, MAPK1, and AR) obtained from the screen. The enrichment analysis indicated that the cAMP, PI3K-Akt, and ErbB signaling pathways may be key signaling pathways in network pharmacology. The molecular docking results showed that sanguinarine, chelerythrine, allocryptopine, and protopine bound well to MAPK3 and JAK2. A comprehensive bioinformatics-based network topology strategy and molecular docking study has elucidated the multi-component synergistic mechanism of action of M. cordata in the treatment of bovine hoof disease, offering the possibility of developing M. cordata as a new source of drugs for hoof disease treatment.

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Role of the JAK-STAT Pathway in Bovine Mastitis and Milk Production

Cited by 42 publications

References 131 publications

Beta-Sitosterol Promotes Milk Protein and Fat Syntheses-Related Genes in Bovine Mammary Epithelial Cells

Beta-Sitosterol Promotes Milk Protein and Fat Syntheses-Related Genes in Bovine Mammary Epithelial Cells

Differential Expression Profiles of lncRNA Following LPS-Induced Inflammation in Bovine Mammary Epithelial Cells

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

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