scholarly journals Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin-Hua Liu ◽  
Zachary A. Graham ◽  
Lauren Harlow ◽  
Jiangping Pan ◽  
Daniella Azulai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Cord Injury ◽  
Fgf21 Expression

Spinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in sham-mice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI.

scholarly journals Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs its Signaling Pathways in Liver and Adipose Tissue in Mice

2021 ◽  
Author(s):  
Xin-Hua Liu ◽  
Zachary A. Graham ◽  
Lauren Harlow ◽  
Jiangping Pan ◽  
Daniella Azulai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Cord Injury ◽  
Fgf21 Expression

AbstractSpinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in shammice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI.

scholarly journals Systemic Administration of Fibroblast Growth Factor 21 Improves the Recovery of Spinal Cord Injury (SCI) in Rats and Attenuates SCI-Induced Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Lin Ye ◽  
Weiyang Ying ◽  
Jiahui Ye ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Functional Recovery ◽  
Nerve Cells ◽  
Systemic Administration ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Cord Injury

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.

233-LB: Spinal Cord Injury Inhibited-FGF21 Signaling Is Associated with Dysregulation of Metabolic Gene Expression in Mouse Liver and Adipose Tissue

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 233-LB
Author(s):  
XIN-HUA LIU ◽  
LAUREN HARLOW ◽  
ZACHARY GRAHAM ◽  
JOSHUA F. YARROW ◽  
KENNETH CUSI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Mouse Liver ◽  
Metabolic Gene ◽  
Metabolic Gene Expression ◽  
Cord Injury

Autologous Adipose Tissue-derived Stromal Cells for Treatment of Spinal Cord Injury

2006 ◽  
Vol 15 (4) ◽  
pp. 583-594 ◽  
Author(s):  
Soo-Kyung Kang ◽  
Myung-Joo Shin ◽  
Jin Sup Jung ◽  
Yong Geun Kim ◽  
Cheul-Hong Kim
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Cord Injury

scholarly journals Adipose tissue derived stromal vascular fraction transplantation can recover spinal cord injury in mice

2016 ◽  
Vol 3 (04) ◽  
pp. 144 ◽  
Author(s):  
Hau Thi-My Lam ◽  
Minh Nguyen-Thu Tran ◽  
Khoa Anh Bui ◽  
Thao Thi-Thu Le ◽  
Khanh Hong-Thien Bui ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adipose Tissue ◽  
Mouse Model ◽  
Platelet Rich Plasma ◽  
Stromal Vascular Fraction ◽  
Paracrine Factors ◽  
Diabetic Ulcer ◽  
Motor Test ◽  
Cord Injury

Introduction: Stem cell therapy is one of the most promising therapies for degenerative diseases and related injuries. Adipose tissue derived stem cells (ADSCs) exhibit some particular properties such as high production of paracrine factors. Indeed, ADSCs have been successfully used to treat diseases, including osteoarthritis, diabetic ulcer, etc. Methods: In this study, ADSCs were used to treat spinal cord injury (SCI) in a mouse model. Non-expanded ADSCs, from stromal vascular fractions (SVFs) isolated from both autologous and allogeneic adipose tissues, were injected into injured sites of mice at a specified dose. The SCI mouse model were generated by transection of spinal cord at vertebrae T8 - T10. After 1 week of transection, mice exhibiting completed SCI were divided into 4 groups: group 1 was control (mice without any treatment), group 2 was placebo (mice treated with platelet rich plasma (PRP)), group 3 was allogeneic SVF transplantation (mice treated with allogeneic SVFs), and group 4 was autologous SVF transplantation (mice treated with autologous SVFs). For the treatment groups, mice were transplanted with 20 µL of activated PRP or/and with 106 cells of SVF (allogeneic or autologous) into the injured position through laminectomy. The recovery of SCI was evaluated by locomotor test, sensory test and sensory-motor test at 5 weeks after transplantation. The histology of the spinal cord also was checked after 5 weeks. Results: The results showed that in all groups with PRP injected with or without SVFs, the inflammation was efficiently controlled. The glial scar as well as myelin defragmentation were clearly reduced. However, a significant improvement of BBB score was only recorded in mice transplanted with autologous SVFs. Conclusion: The results of our study show that autologous SVF transplantation in combination with PRP can be a promising therapy for SCI.

Increased Basic Fibroblast Growth Factor Expression Following Contusive Spinal Cord Injury

1996 ◽  
Vol 141 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Italo Mocchetti ◽  
Stuart J. Rabin ◽  
Anna M. Colangelo ◽  
Scott R. Whittemore ◽  
Jean R. Wrathall
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Cord Injury ◽  
Factor Expression ◽  
Growth Factor Expression ◽  
Contusive Spinal Cord Injury

Inflammatory Response and Cell Apoptosis are Inhibited by Indirubin-3′-Oxime via PI3K/Akt Pathway in Rat Model of Spinal Cord Injury ​

2020 ◽  
Author(s):  
Yan Zhu ◽  
Lixue Wu ◽  
Qiuxiang Zhou ◽  
Yueyue Yan ◽  
Jinlong Qu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Serum Levels ◽  
Motor Dysfunction ◽  
Akt Phosphorylation ◽  
Treatment Groups ◽  
Ppar Γ ◽  
Post Surgery ◽  
Cord Injury

Abstract Spinal cord injury (SCI) main cause of motor dysfunction results in loss of feelings partially or completely. The current study investigated indirubin-3′-oxime (IR3O) for treatment of SCI in rat model and evaluated the related mechanism. Rats in model SCI and ID30 groups were subjected to laminectomy at 8th thoracic vertebra level. Vertebral column was secured by clamping T6 and T10 and SCI model was established by dripping a hammer. Treatment groups received 0.25, 0.5, 0.75 and 1.0 mg/kg doses of ID30 daily for 2-weeks post-surgery. Treatment with ID30 effectively improved BBB score in rats with SCI in dose-based manner. Accumulation of water in spinal cord tissues was alleviated significantly on treatment of SCI rats with ID30. ID30 treatment significantly alleviated SCI mediated higher serum levels of TNF-α and cytokines (IL-1β and IL-6) in SCI rats. In ID30 treated SCI rats SOD, CAT and GSH activities were significantly alleviated. The SCI mediated increased cleaved caspase-3 and -9 levels were alleviated by ID30 treatment significantly. Moreover, ID30 treatment suppressed SCI mediated elevation of PGE2, COX‑2 levels and significantly (P<0.05) elevated PPAR-γ expression. The ID30 treatment of SCI rats significantly (P<0.05) elevated PI3K and Akt phosphorylation. Thus, ID30 inhibited edema and improved BBB score in rats with SCI by targeting pro-inflammatory cytokines and oxidative response. Moreover, in SCI rats ID30 treatment down-regulated apoptotic proteins, promoted PPAR-γ activation and elevated PI3K/Akt phosphorylation. Thus, ID30 has potential to be studied further for development of therapeutic strategy for SCI.

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