BRCC36 promotes intestinal mucosal barrier injury caused by BMP2 after ischemia-reperfusion via inhibiting PPARγ signaling

2021 ◽  
Author(s):  
Jin-Ming Zhang ◽  
Kun-Nan Wang ◽  
Yun Zhang ◽  
Jun-Ze Zhang ◽  
Xin-Pu Yuan ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Bone Morphogenetic Protein 2 ◽  
Mucosal Barrier ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intestinal Mucosal Barrier ◽  
Morphogenetic Protein ◽  
Mucosal Barrier Injury ◽  
Brca1 Brca2 ◽  
Intestinal Ischemia Reperfusion

Abstract As one of the most common pathological changes in trauma and surgery practice, intestinal ischemia-reperfusion (I/R) injury is regarded as a major precipitating factor in the occurrence and development of fatal diseases. BRCA1-BRCA2-containing complex subunit 36 (BRCC36), a deubiquitinase, has been proved important in a variety of pathophysiological processes such as DNA repair, cell cycle regulation, tumorigenesis and inflammatory response. However, the effect of BRCC36 on intestinal mucosal barrier injury after I/R has not been fully elucidated. Our research found that BRCC36 aggravated intestinal mucosal barrier injury caused by BMP2 (Bone morphogenetic protein 2) after I/R by downregulating PPARγ (Peroxisome proliferator-activated receptor-γ) signaling. These results suggested that BRCC36/PPARγ axis might serve as a potential therapeutic target for preventing intestinal mucosal barrier injury after I/R.

scholarly journals Association Between BMP2 Functional Polymorphisms and Sheep Tail Type

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 739
Author(s):  
Zengkui Lu ◽  
Jianbin Liu ◽  
Jilong Han ◽  
Bohui Yang
Keyword(s):  
Tail Length ◽  
Cellular Level ◽  
Fat Deposition ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
Functional Polymorphisms ◽  
Genotype Frequencies ◽  
Morphogenetic Protein

Bone morphogenetic protein 2 (BMP2) is strongly selected in both fat-tailed and thin-tailed sheep and may be a candidate gene for sheep tail type selection. However, the mechanism of action of BMP2 in sheep tail fat deposition remains unclear. This study investigated genetic variation and haplotype combinations of the BMP2 gene in sheep with different tail types, aiming to reveal the molecular mechanism of BMP2 in sheep tail fat deposition. We detected a total of three single nucleotide polymorphisms (SNPs) (g.48401619 T > A, g.48401272 C > A, and g.48401136 C > T) among 533 sheep. The alleles and genotype frequencies of these SNPs were in Hardy–Weinberg equilibrium and showed significant correlations with tail length. Linkage disequilibrium existed between the g.48401272 C > A and g.48401136 C > T sites, where CACT was the predominant genotype. At the cellular level, the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) were upregulated after BMP2 overexpression; there were significantly higher levels of PPARγ than controls at 0 d and 1 d, and of LPL than controls at 1 d and 7 d. These results indicate that the BMP2 gene may participate in sheep tail fat deposition and could be used for molecular-marker-assisted selection of sheep tail type.

scholarly journals Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6065-6075 ◽  
Author(s):  
Buer Sen ◽  
Zhihui Xie ◽  
Natasha Case ◽  
Meiyun Ma ◽  
Clinton Rubin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Glycogen Synthase ◽  
Mechanical Strain ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Glycogen Synthase Kinase 3Β ◽  
Peroxisome Proliferator Activated Receptor ◽  
Morphogenetic Protein ◽  
Adiponectin Mrna

The ability of exercise to decrease fat mass and increase bone mass may occur through mechanical biasing of mesenchymal stem cells (MSCs) away from adipogenesis and toward osteoblastogenesis. C3H10T1/2 MSCs cultured in highly adipogenic medium express peroxisome proliferator-activated receptor γ and adiponectin mRNA and protein, and accumulate intracellular lipid. Mechanical strain applied for 6 h daily inhibited expression of peroxisome proliferator-activated receptor γ and adiponectin mRNA by up to 35 and 50%, respectively, after 5 d. A decrease in active and total β-catenin levels during adipogenic differentiation was entirely prevented by daily application of mechanical strain; furthermore, strain induced β-catenin nuclear translocation. Inhibition of glycogen synthase kinase-3β by lithium chloride or SB415286 also prevented adipogenesis, suggesting that preservation of β-catenin levels was important to strain inhibition of adipogenesis. Indeed, mechanical strain inactivated glycogen synthase kinase-3β, which was preceded by Akt activation, indicating that strain transmits antiadipogenic signals through this pathway. Cells grown under adipogenic conditions showed no increase in osteogenic markers runt-related transcription factor (Runx) 2 and osterix (Osx); subsequent addition of bone morphogenetic protein 2 for 2 d increased Runx2 but not Osx expression in unstrained cultures. When cultures were strained for 5 d before bone morphogenetic protein 2 addition, Runx2 mRNA increased more than in unstrained cultures, and Osx expression more than doubled. As such, mechanical strain enhanced MSC potential to enter the osteoblast lineage despite exposure to adipogenic conditions. Our results indicate that MSC commitment to adipogenesis can be suppressed by mechanical signals, allowing other signals to promote osteoblastogenesis. These data suggest that positive effects of exercise on both fat and bone may occur during mesenchymal lineage selection.

scholarly journals The Role of ATF-2 Family Transcription Factors in Adipocyte Differentiation: Antiobesity Effects of p38 Inhibitors

2009 ◽  
Vol 30 (3) ◽  
pp. 613-625 ◽  
Author(s):  
Toshio Maekawa ◽  
Wanzhu Jin ◽  
Shunsuke Ishii
Keyword(s):  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Physiological Role ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
P38 Inhibitor ◽  
Morphogenetic Protein

ABSTRACT ATF-2 is a member of the ATF/CREB family of transcription factors and is activated by stress-activated protein kinases, such as p38. To analyze the physiological role of ATF-2 family transcription factors, we have generated mice with mutations in Atf-2 and Cre-bpa, an Atf-2-related gene. The trans-heterozygotes of both mutants were lean and had reduced white adipose tissue (WAT). ATF-2 and CRE-BPa were required for bone morphogenetic protein 2 (BMP-2)-and p38-dependent induction of peroxisome proliferator-activated receptor γ2 (PPARγ2), a key transcription factor mediating adipocyte differentiation. Since stored fat supplies have been recognized as a possible target for antiobesity treatments, we tested whether inhibition of the p38-ATF-2 pathway suppresses adipocyte differentiation and leads to reduced WAT by treating mice with a p38 inhibitor for long periods of time. High-fat diet (HFD)-induced obesity was significantly reduced in mice fed the p38 inhibitor. Furthermore, the p38 inhibitor alleviated HFD-induced insulin resistance. In p38 inhibitor-treated mice, macrophage infiltration into WAT was reduced and the tumor necrosis factor alpha (TNF-α) levels were lower than control mice. Thus, p38 inhibitors may provide a novel antiobesity treatment.

scholarly journals Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ

2016 ◽  
Vol 311 (4) ◽  
pp. R676-R688 ◽  
Author(s):  
Ahmad Hanif ◽  
Matthew L. Edin ◽  
Darryl C. Zeldin ◽  
Christophe Morisseau ◽  
Mohammed A. Nayeem
Keyword(s):  
Epoxide Hydrolase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Hyperemia ◽  
Soluble Epoxide Hydrolase ◽  
Mouse Heart ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH+/+, sEH−/− mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32% higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC-MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline ( P < 0.001) and 5.6-fold higher post-ischemia ( P < 0.001) in sEH−/− compared with sEH+/+ mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold ( P < 0.01) and 3.7-fold ( P < 0.001) higher, respectively in sEH−/− compared with sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% ( P < 0.01) in sEH−/− vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids were not significantly different between the two strains ( P > 0.05), but were decreased postischemia in both groups ( P = 0.02, P = 0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome proliferator-activated receptor gamma (PPARγ) was demonstrated using a PPARγ-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+ ( P < 0.001) and 33% in sEH−/− mice ( P < 0.01), and a PPARγ-agonist (rosiglitazone), which increased repayment volume by 37% in both sEH+/+ ( P = 0.04) and sEH−/− mice ( P = 0.04). l-NAME attenuated CRH in both sEH−/− and sEH+/+. These data demonstrate that genetic deletion of sEH resulted in an altered oxylipin profile, which may have led to an enhanced CRH response.

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