Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

Zhang, Rui; Ma, Huimin; Gao, Yuan; Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial; Liu, Xiaolong; Ge, Gaoxiang

doi:10.1371/journal.pgen.1007211

Cited by 26 publications

(26 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…I-WAT and E-WAT were washed with PBS, cut into small pieces, and digested with 1 mg/mL Collagenase (Worthington, Lakewood, New Jersey) at 37°C for 60 minutes. SVF cell culture, FACS analyses, and adipogenic induction were performed as described [ 40 , 41 ]. For PDGF and VP treatment experiments, SVF cells were treated with PDGF or VP for 4 days before FACS analyses and adipogenic induction.…”

Section: Methodsmentioning

confidence: 99%

FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

et al. 2018

Self Cite

View full text Add to dashboard Cite

Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis.

show abstract

Section: Methodsmentioning

confidence: 99%

FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that mammary epithelial cells (MECs) play key roles in milk protein and lipid biosynthesis [ 1 – 3 ]. During lactation, MECs secrete large quantities of milk proteins, notably caseins.…”

Section: Introductionmentioning

confidence: 99%

Chi-miR-3031 regulates beta-casein via the PI3K/AKT-mTOR signaling pathway in goat mammary epithelial cells (GMECs)

et al. 2018

View full text Add to dashboard Cite

BackgroundMicroRNAs can regulate gene expression at the posttranscriptional level through translational repression or target degradation. Our previous investigations examined the differential expression levels of chi-miR-3031 in caprine mammary gland tissues in colostrum and common milk stages.ResultsThe present study detected the role of chi-miR-3031 in the lactation mechanisms of GMECs. High-throughput sequencing was used to analyze transcriptomic landscapes of GMECs transfected with chi-miR-3031 mimics (MC) and a mimic negative control (NC). In the MC and NC groups, we acquired 39,793,503 and 36,531,517 uniquely mapped reads, respectively, accounting for 85.85 and 81.66% of total reads. In the MC group, 180 differentially expressed unigenes were downregulated, whereas 157 unigenes were upregulated. KEGG pathway analyses showed that the prolactin, TNF and ErbB signaling pathways, including TGFα, PIK3R3, IGF2, ELF5, IGFBP5 and LHβ genes, played important roles in mammary development and milk secretion. Results from transcriptome sequencing, real-time PCR and western blotting showed that chi-miR-3031 suppressed the expression of IGFBP5 mRNA and protein. The expression levels of β-casein significantly increased in the MC and siRNA-IGFBP5 groups. We observed that the down-regulation of IGFBP5 activated mTOR at the Ser2448 site in GMECs transfected with MC and siRNA-IGFBP5. Previous findings and our results showed that chi-miR-3031 activated the PI3K-AKT-mTOR pathway and increased β-casein expression by down-regulating IGFBP5.ConclusionsThese findings will afford valuable information for improving milk quality and contribute the development of potential methods for amending lactation performance.Electronic supplementary materialThe online version of this article (10.1186/s12917-018-1695-6) contains supplementary material, which is available to authorized users.

show abstract

“…Automated scoring and quantitative evaluation of DAB stained IHC images are performed using open source IHC Profiler Plugin 66 in ImageJ software. H-score was calculated by adding the percentage of high positive (×3), positive (×2), and low positive cells (×1) as described 67 . Hscore has a possible range of 0-300.…”

Section: Histological and Immunohistochemical Stainingmentioning

confidence: 99%

Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis

Cao

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Liver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen α5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen α5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.

show abstract

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

Cited by 26 publications

References 70 publications

FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis

Chi-miR-3031 regulates beta-casein via the PI3K/AKT-mTOR signaling pathway in goat mammary epithelial cells (GMECs)

Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis

Contact Info

Product

Resources

About