A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation

Otani, Masataka; Furukawa, Souhei; Wakisaka, Satoshi; Maeda, Takashi

doi:10.1007/s11010-015-2531-y

Cited by 26 publications

(23 citation statements)

References 39 publications

(58 reference statements)

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“…While, the top 3 genes induced in miR106b-93-25 −/− ischemic-muscle (compared to WT) CXCL2 (50,51) , IRG1 (34,52) and GM3893 were intimately associated with immune responses (with the exception of GM3893, a long non-coding RNA) the top 3 downregulated genes C1QTNF3 (53) , MYH3 (54,55) and ACTC1 (56,57) were closely associated with skeletal muscle function. These data clearly indicated an inverse correlation between genes that regulate immune cell function and skeletal muscle perfusion-recovery in miR106b-93-25 −/− ischemic-muscle.…”

Section: Discussionmentioning

confidence: 99%

A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

et al. 2017

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Background Currently no therapies exist for treating, and improving outcomes in patients with severe peripheral arterial disease (PAD). MicroRNA93 (miR93) has been shown to favorably modulate angiogenesis and reduce tissue loss in genetic PAD models. However, the cell specific function, downstream mechanisms or signaling involved in miR93 mediated ischemic muscle neovascularization is not clear. Macrophages were best known to modulate arteriogenic response in PAD and the extent of arteriogenic response induced by macrophages is dependent on greater M2 to M1-activation/polarization state. In the current study, we identified a novel mechanism by which miR93 regulates macrophage-polarization to promote angiogenesis and arteriogenesis to revascularize ischemic muscle in experimental-PAD. Methods In vitro (macrophages, endothelial cells, skeletal muscle cells under normal and hypoxia serum starvation (HSS) conditions) and in vivo experiments in preclinical-PAD models (unilateral femoral artery ligation and resection)) were conducted to examine the role of miR93-interferon regulatory factor-9 (IRF9)-immune responsive gene-1 (IRG1)-itaconic acid pathway in macrophage-polarization, angiogenesis, arteriogenesis and perfusion recovery. Results In vivo, compared to wild type (WT) controls, miR106b-93-25 cluster deficient mice (miR106b-93-25−/−) showed decreased angiogenesis and arteriogenesis correlating with increased M1-like-macrophages following experimental-PAD. Intra-muscular delivery of miR93 in miR106b-93-25−/− PAD mice increased angiogenesis, arteriogenesis, the extent of perfusion which correlated with more M2-like-macrophages in the proximal and distal hind-limb muscles. In vitro, miR93 promotes and sustains M2-like-polarization even under M1-like-polarizing conditions (HSS). Delivery of bone marrow derived macrophages from miR106b-93-25−/− to WT ischemic-muscle decreased angiogenesis, arteriogenesis and perfusion, while transfer of wild-type macrophages to miR106b-93-25−/− had the opposite effect. Systematic analysis of top-differentially upregulated genes from RNA-sequencing between miR106b-93-25−/− and WT ischemic-muscle showed that miR93 regulates IRG1 function to modulate itaconic acid production and macrophage-polarization. 3′UTR luciferase-assays performed to determine whether IRG1 is a direct target of miR93 revealed that IRG1 is not a miR93 target but IRF9 that can regulate IRG1-expression is a miR93 target. In vitro, increased expression of IRF9, IRG1 and itaconic acid treatment significantly decreased endothelial angiogenic potential. Conclusion We conclude that miR93 inhibits IRF9 to decrease IRG1-itaconic acid production to induce M2-like-polarization in ischemic muscle to enhance angiogenesis, arteriogenesis and perfusion recovery in experimental-PAD.

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Section: Discussionmentioning

confidence: 99%

A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

et al. 2017

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“…There is a lot of evidence to indicate that ERK1/2 pathway is involved in regulating the proliferation of muscle cells272829. To gain insight into the mechanisms by which Akirin2 stimulates the proliferation and differentiation of porcine skeletal muscle satellite cells, we evaluated the signaling events.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested that the effect of MAPK on muscle cells differentiation is controversial. Some studies suggest that activation of the ERK pathway prevents skeletal muscle differentiation293031, and other studies believe that it functions at two stages of skeletal muscle differentiation1032. However, recent data indicate that ERK1/2 may positively regulate myogenic differentiation62833.…”

Section: Discussionmentioning

confidence: 99%

Akirin2 regulates proliferation and differentiation of porcine skeletal muscle satellite cells via ERK1/2 and NFATc1 signaling pathways

Chen

Luo

Huang

et al. 2017

Sci Rep

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Akirin2, a novel nuclear factor, plays an important role in myogenesis. To investigate the role of Akirin2 in proliferation and differentiation of porcine skeletal muscle satellite cells, Akirin2 overexpression and Akirin2 silence technologies were employed. Our results showed that overexpression of Akirin2 markedly enhanced the proliferation and differentiation of porcine skeletal muscle satellite cells, whereas silencing of Akirin2 got the opposite results. Furthermore, our results showed that Akirin2 affected proliferation and differentiation of porcine skeletal muscle satellite cells through extracellular-signal regulated kinase-1/2 (ERK1/2) and NFATc1 signaling pathways. These results indicate that Akirin2 can effectively promote skeletal muscle satellite cells proliferation and differentiation, acting through ERK1/2- and NFATc1-dependent mechanisms.

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“…Among the CTRPs, CTRP3, also known as CORS26/cartducin, was first identified as a growth plate cartilage-derived secretory protein (Maeda et al, 2001). It has also been reported to be expressed in myotubes (Otani et al, 2015), adipocytes (Sch€ affler et al, 2003), and adipose tissues (Wong et al, 2008). Several studies using animal models have revealed that CTRP3 administration decreases blood glucose levels and suppresses hepatic gluconeogenic gene expression in normal and insulin-resistant ob/ob mice (Peterson et al, 2010), and that it reduces hepatic triglyceride levels in dietinduced obese (DIO) mice .…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF‐related protein 3 expression and effects on adipocyte differentiation of 3T3‐L1 cells

Nishimoto

Yamamoto

Furukawa

et al. 2016

Cell Biology International

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Adipose tissue-derived adipokines influence a number of organs critical for energy homeostasis and metabolism. One of the most extensively studied adipokines is adiponectin, which exerts anti-diabetic, anti-inflammatory, and anti-atherogenic functions on various cell types. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 reduces hepatic triglyceride levels in diet-induced obese (DIO) mice. However, the physiological role of CTRP3 in adipocytes is largely unknown. In the course of our investigation of expression profiles of CTRPs during adipocyte differentiation, we found that CTRP3 expression pattern is different from that previously reported. Therefore, we examined the effect of CTRP3 on adipogenesis using 3T3-L1 cells. The expression level of CTRP3 was markedly decreased during the differentiation of 3T3-L1 cells. Recombinant CTRP3 (rCTRP3) treatment significantly reduced intracellular lipid content and decreased expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, and fatty acid binding protein 4 (FABP4) in 3T3-L1 cells. Furthermore, rCTRP3 induced the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and Akt in differentiated 3T3-L1 adipocytes. These results suggest that CTRP3 may negatively regulate lipid metabolism during adipocyte differentiation.

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A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation

Cited by 26 publications

References 39 publications

A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

Akirin2 regulates proliferation and differentiation of porcine skeletal muscle satellite cells via ERK1/2 and NFATc1 signaling pathways

C1q/TNF‐related protein 3 expression and effects on adipocyte differentiation of 3T3‐L1 cells

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