Bifunctional role of ephrin A1‐Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells

Kang, Min‐Kyung; Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W.; Song, Gwonhwa

doi:10.1002/jcp.26131

Cited by 20 publications

(14 citation statements)

References 53 publications

(67 reference statements)

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“…Previous studies conjectured that regulating ER stress may be important for development of the bovine mammary gland, as the expression of the ER stress component genes changes dynamically in bovine mammary tissue during lactation (Invernizzi et al, 2012). To the best of our best knowledge, along with our previous study, this is the first report of a ligand, CCL2, that attenuates ER stress in bovine mammary epithelial cells (Kang et al, 2017).…”

Section: Discussionsupporting

confidence: 50%

C-C motif chemokine ligand 2 induces proliferation and prevents lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial cells

Yang

Lim

Bae

et al. 2018

Journal of Dairy Science

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C-C motif chemokine ligand 2 (CCL2) is a small chemokine which belongs to the CC-type chemokine family, and has chemoattractant activity for recruitment of monocytes to sites of inflammation. Overexpressed CCL2 binding to its receptor C-C chemokine receptor 2 increases the risk of breast cancer in humans, but its effects on proliferation of bovine mammary epithelial cells is not known. Maintaining a high level of proliferative activity in bovine mammary epithelial cells during lactation is important for improving milk yield and can benefit the dairy industry economically. In the present study, we demonstrated that CCL2 induces proliferation of MAC-T cells, a bovine mammary epithelial cell line, and stimulates progression of the cell cycle through stimulation of expression of cyclin D1. Moreover, CCL2 activates phosphoinositide 3-kinase (PI3K)/AKT [AKT, P70-S6 kinase 1 (P70S6K), ribosomal protein S6 (S6)] and mitogen activated protein kinase (MAPK) [extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and P38] pathways, which are involved in proliferation of MAC-T cells, as evidenced by co-treatment of MAC-T cells with pharmacological inhibitors of cell signaling transcription factors including Wortmannin, U0126, and SP600125. The CCL2 in MAC-T cells attenuates endoplasmic reticulum stress induced by tunicamycin, suggesting that CCL2 regulates intracellular synthesis of proteins and lipids and prevents activation of apoptotic pathways initiated in response to endoplasmic reticulum stress. Furthermore, CCL2 is involved in alleviating lipopolysaccharide (LPS)-induced inflammatory responses in MAC-T cells by reducing LPS-induced expression of IL8, IL6, and nuclear factor kappa B subunit 1 (NFKB1). Collectively, CCL2 is a novel target for improving the quantity and quality of milk from cows through stimulation of proliferation on mammary epithelial cells and attenuation of LPS-induced inflammatory responses.

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Section: Discussionsupporting

confidence: 50%

C-C motif chemokine ligand 2 induces proliferation and prevents lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial cells

Yang

Lim

Bae

et al. 2018

Journal of Dairy Science

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“…This is supported by reports that the expression of ephrin-B2, EphA2 and ephrin-A1 is increased in cerebellar Purkinje cells of EphA4 knockout mice, which likely compensate for the function of EphA4 in patterning the Purkinje cells compartment 38 . Moreover, members of the Eph/ephrin family are involved in regulation of cell death in the brain, such as ephrin-A1 39 , ephrin-A5, EphA7 40 and EphB2 41 . Recently, Ling and colleagues reported that reduction of mRNA expression of EphA4 in the CNS by antisense oligonucleotides (ASO) did not result in significant improvement in functional performance 42 .…”

Section: Discussionmentioning

confidence: 99%

Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1G93A ALS mouse model

Zhao

Cooper

Boyd

et al. 2018

Sci Rep

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Amyotrophic lateral sclerosis (ALS) is an untreatable, progressive, neurodegenerative disease specifically affecting motor neurons. Recently, the tyrosine kinase receptor EphA4 was directly implicated in ALS disease progression. We report that a long-lived mutated form of the EphA4 antagonist EphA4-Fc (mutEphA4-Fc), which blocks EphA4 binding to its ligands and inhibits its function, significantly improved functional performance in SOD1G93A ALS model mice, as assessed by rotarod and hind-limb grip strength tests. Further, heterozygous motor neuron-specific EphA4 gene deletion in SOD1G93A mice promoted significant improvement in functional performance during the disease course and a delay in disease onset relative to control mice. Importantly, mice in the heterozygous deletion group showed significantly improved survival of motor neurons and architecture of endplates of neuromuscular junctions compared with control and homozygous EphA4-deletion groups. Our novel results show that EphA4 signalling directly regulates motor neuron survival and that mutEphA4-Fc is a promising therapeutic candidate to slow disease progression in ALS.

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“…Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis (Deb et al, 2014). Eph A-ephrin A1 (EPHA1) system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals (Kang et al, 2018). Fc-g receptors (FCGR) play a role in the response to rituximab in autoimmune -receptor III a (FCGR3A) diseases and is a very important factor of immune system (Robledo et al, 2012).…”

Section: Grb10 Calcr Trpv6mentioning

confidence: 99%

Evaluation of runs of homozygosity and genomic inbreeding in Holstein cattle from Colombia

Zambrano¹,

Florez²,

Ríos³

et al. 2020

Semina: Ciênc. Agrár.

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Traditional selection programs for dairy cattle, based on quantitative principles, have worked well and allowed strong selection processes in the world over many decades. The objectives of this work were to estimate linkage disequilibrium (LD) levels at varying SNPs densities, to evaluate the effective population size of Holstein cattle, to characterize runs of homozygosity (ROH) distribution through Holstein cattle from Nariño and, to estimate and compare inbreeding coefficient (F) based on genomic markers information, runs of homozygosity (FROH), genomic relationship matrix (FGRM), and excess of homozygous (FSNP). After quality control, the dataset used was composed of 606 Holstein animals and 22200 SNP markers. PLINK program was used to identify LD, Ne, ROH segment and FROH and FSNP, FGRM was calculated with BLUPF90 family of programs. The average of r2 in all chromosomes was 0.011, the highest r2 was found in BTA3 (0.0323), and the lowest in BTA12 (0.0039). 533 ROH segments were identified in 319 animals; findings obtained in this study suggest that on average 0,28% of Holstein genome is autozygous. Total length of ROH was composed mostly of small segments (ROH1-4Mb and ROH4-8Mb). These segments accounted for approximately 96%, while larger ROH (ROH>8Mb) were 3.37% of all ROH detected. Inbreeding averages FROH, FSNP and FGRM methodologies were 0.28%, 3.11% and 3.36% respectively. The Pearson’s correlation among these different F values was: 0.49 (FROH-FSNP), 0.25 (FROH-FGRM), 0.22 (FSNP-FGRM). The distribution of ROH shared regions identified on 19 autosome chromosomes, cover a relevant number of genes inside these ROH. Our result evidenced lowest LD extension levels compared with other Holstein populations; inbreeding results suggest that FGRM and FSNP may be useful estimators of individual autozygosity in Holstein from Colombia. Genes related with production and reproduction were found, but the most important are the two that may be related to adaptation to Colombian high tropics. This work is a pioneer and be the starting point for programs of genetic improvement and genomic population studies in the country and mainly in high tropic areas where the dairy breeds have an important production.

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Bifunctional role of ephrin A1‐Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells

Cited by 20 publications

References 53 publications

C-C motif chemokine ligand 2 induces proliferation and prevents lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial cells

C-C motif chemokine ligand 2 induces proliferation and prevents lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial cells

Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1G93A ALS mouse model

Evaluation of runs of homozygosity and genomic inbreeding in Holstein cattle from Colombia

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