αMSH inhibits adipose inflammation via reducing FoxOs transcription and blocking Akt/JNK pathway in mice

Liu, Guannv; Li, Meihang; Saeed, Muhammad; Ren, Qian; Sun, Cheng

doi:10.18632/oncotarget.17465

Cited by 17 publications

(25 citation statements)

References 56 publications

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“…Previously, the BMP/Smad and Akt/MAPK/NF-κB pathways were found to contribute to rh-SHH-induced osteoblastic or cementoblastic differentiation [23], and a stepwise pathway involving Akt/JNK or Akt-MAPK/ERK was demonstrated to regulate cell inflammation, an undifferentiated state and viability [25,59]. These findings are consistent with our data that JNK activation induced by M2 Mφs was inhibited by the addition of Akt inhibitor (Fig.…”

Section: Stem Cellssupporting

confidence: 93%

“…Given that the Wnt/β-catenin, Akt, TGF-β/Smad, BMP/Smad, and MAPK pathways have been demonstrated to regulate the osteogenesis/cementogenesis process [20][21][22][23][24][25][26][27][28], key genes involved in the above pathways were selected to screen the potential pathways that regulate M2 Mφ-enhanced cementoblastic differentiation. When the expression of the selected genes in CM-M2-treated PDLSCs (M2 group) and untreated PDLSCs (Control group) was analyzed using qRT-PCR, the pathway-related genes that were differentially expressed between the two groups were plotted in a heatmap (Fig.…”

Section: Potential Pathways Involved In M2 Mφ-enhanced Cementoblasticmentioning

confidence: 99%

“…The roles of the Akt and JNK pathways in M2 subset-mediated cementoblastic differentiation were further clarified by using the Akt inhibitor MK-2206 (MedChem Express, Monmouth Junction, NJ) and the JNK inhibitor SP600125 (MedChem Express) [25,28]. Although CM-M2 treatment increased mRNA expression levels of BSP, CEMP-1, and CAP in PDLSCs, the addition of MK-2206 ( Fig.…”

Section: Clarification Of the Roles Of The Akt And Jnk Pathways In M2mentioning

confidence: 99%

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M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

Kong

et al. 2019

Stem Cells

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Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP‐1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium‐based and Transwell‐based coculture systems. Furthermore, the potential pathways and cyto‐/chemokines involved in Mφ‐mediated cementoblastic differentiation were screened and identified. In both systems, M2 subsets increased cementoblastic differentiation‐related gene/protein expression levels in cocultured PDLSCs, induced more PDLSCs to differentiate into polygonal and square cells, and enhanced alkaline phosphatase activity in PDLSCs. Furthermore, Akt and c‐Jun N‐terminal Kinase (JNK) signaling was identified as a potential pathway involved in M2 Mφ‐enhanced PDLSC cementoblastic differentiation, and cyto‐/chemokines (interleukin (IL)‐10 and vascular endothelial growth factor [VEGF]) secreted by M2 Mφs were found to be key players that promoted cell cementoblastic differentiation by activating Akt signaling. Our data indicate for the first time that Mφs are key modulators during PDLSC cementoblastic differentiation and are hence very important for the regeneration of multiple periodontal tissues, including the cementum. Although the Akt and JNK pathways are involved in M2 Mφ‐enhanced cementoblastic differentiation, only the Akt pathway can be activated via a cyto‐/chemokine‐associated mechanism, suggesting that players other than cyto‐/chemokines also participate in the M2‐mediated cementoblastic differentiation of PDLSCs. Stem Cells 2019;37:1567–1580

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Section: Stem Cellssupporting

confidence: 93%

Section: Potential Pathways Involved In M2 Mφ-enhanced Cementoblasticmentioning

confidence: 99%

Section: Clarification Of the Roles Of The Akt And Jnk Pathways In M2mentioning

confidence: 99%

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M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

Kong

et al. 2019

Stem Cells

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“…In fact, the exosomal release from these cells and the consequent exosomes-induced node and tube formation in the HUVEC were significantly reduced by ARPE-19 treatment with PG-901, a melanocortin receptor MCR 5 agonist. The MCR 5 receptor plays a role in glucose metabolismand inflammation-based pathologies [29,30], and is expressed in retinal pigment epithelial cells [4]. Human studies showed that single-nucleotide polymorphism in the MCR 5 was associated with type 2 diabetes in obese subjects, while experimental in vivo and ex vivo studies demonstated that a glucose uptake in skeletal muscles driven by α-MSH is markedly reduced in MCR 5 KO mice.…”

Section: Discussionmentioning

confidence: 99%

ARPE-19-derived VEGF-containing exosomes promote neovascularization in HUVEC: the role of the melanocortin receptor 5

Maisto¹,

Oltra

Vidal-Gil

et al. 2019

Cell Cycle

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ARPE-19 retinal pigment epithelial cells cultured in a medium containing 35 mM D-glucose led to an augmented ROS formation and release of vascular endothelial factor (VEGF)-containing exosomes compared to ARPE-19 cells cultured in a medium containing 5 mM D-glucose (standard medium). Exposing these cells to the melanocortin 5 receptor agonist (MCR 5) PG-901 (10 −10 M), for 9 d reduced ROS generation, the number of exosomes released and their VEGF content. In contrast, incubating the cells with the melanocortin receptor MCR 1 agonist BMS-470539 (10 −5 M) or with the mixed MCR 3/4 agonist MTII (0.30 nmol) did not produce any significant decrease in ROS levels. ARPE-19-derived VEGFcontaining exosomes promoted neovascularization in human umbilical vein endothelial cells (HUVEC), an effect that was markedly reduced by PG-901 (10 −10 M) but not by the MCR 3/4 agonist MTII (0.30 nmol) or the MCR 1 agonist BMS-470539 (10 −5 M). The MCR 5-related action in the ARPE-19 cells was accompanied by the increased expression of two coupled factors, cytochrome p4502E1 (CYP2E1) and nuclear factor kappa b (Nf-κB). These are both involved in high glucose signalling, in ROS generation and, interestingly, were reduced by the MCR 5 agonist in the ARPE-19 cells. Altogether, these data suggest that MCR 5 is a modulator of the responses stimulated by glucose in ARPE-19 cells, which might possibly be translated into a modulation of the retinal pigment epithelium response to diabetes in vivo.

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“…The dual-luciferase reporter assay procedure was performed as described in Liu et al (27). The fragment of the 3′-untranslated region (UTR) of Wnt3a for miR-103 and miR-107 was synthesized and cloned into the region of the PGL3 vector.…”

Section: Reporter Constructs and Dual-luciferase Reporter Assaysmentioning

confidence: 99%

miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes

Zhang

Saeed

et al. 2018

Journal of Lipid Research

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Both miR-103 and miR-107 have been demonstrated to restrain cell proliferation and regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocyte apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocyte apoptosis. We found that miR-103/107 aggravated endoplasmic reticulum (ER) stress-mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted WNT family member 3a (Wnt3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress-mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes. Moreover, bioinformatics and luciferase assays indicated that activating transcription factor (ATF)6 is a key player linking miR-103/107-induced ER stress to apoptosis. is regulated by lymphoid enhancer-binding factor 1, a transcription factor downstream of the Wnt3a/β-catenin signaling pathway, and ATF6 binds to the B-cell lymphoma 2 () promoter to regulate apoptosis further. In conclusion, miR-103/107 promoted ER stress-mediated apoptosis by targeting the Wnt3a/β-catenin/ATF6 signaling pathway in preadipocytes. This study revealed that the miR-103/107-Wnt3a/β-catenin-ATF6 pathway is critical to the progression of apoptosis in preadipocytes, which suggested that approaches to activate miR-103/107 could potentially be useful as new therapies for treating obesity and metabolic syndrome-related disorders.

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αMSH inhibits adipose inflammation via reducing FoxOs transcription and blocking Akt/JNK pathway in mice

Cited by 17 publications

References 56 publications

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

ARPE-19-derived VEGF-containing exosomes promote neovascularization in HUVEC: the role of the melanocortin receptor 5

miR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes

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