scholarly journals Bionic microenvironment-inspired synergistic effect of anisotropic micro-nanocomposite topology and biology cues on peripheral nerve regeneration

2021 ◽  
Vol 7 (28) ◽  
pp. eabi5812
Author(s):  
Guicai Li ◽  
Tiantian Zheng ◽  
Linliang Wu ◽  
Qi Han ◽  
Yifeng Lei ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Transforming Growth Factor ◽  
Synergistic Effects ◽  
Peripheral Nerve Regeneration ◽  
Transforming Growth Factor Β ◽  
Signal Pathways ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Promising Application

Anisotropic topographies and biological cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, their synergetic influence on injured peripheral nerve is rarely reported. In the present study, we constructed a bionic microenvironment-inspired scaffold integrated with both anisotropic micro-nanocomposite topographies and IKVAV peptide. The results showed that both the topographies and peptide displayed good stability. The scaffolds could effectively induce the orientation growth of Schwann cells and up-regulate the genes and proteins relevant to myelination. Last, three signal pathways including the Wnt/β-catenin pathway, the extracellular signal–regulated kinase/mitogen-activated protein pathway, and the transforming growth factor–β pathway were put forward, revealing the main path of synergistic effects of anisotropic micro-nanocomposite topographies and biological cues on neuroregeneration. The present study may supply an important strategy for developing functional of artificial nerve implants.

Synergistic effects of dual-presenting VEGF- and BDNF-mimetic peptide epitopes from self-assembling peptide hydrogels on peripheral nerve regeneration

Nanoscale ◽  
2019 ◽  
Vol 11 (42) ◽  
pp. 19943-19958 ◽  
Author(s):  
Jiaju Lu ◽  
Xiaoqing Yan ◽  
Xun Sun ◽  
Xuezhen Shen ◽  
Heyong Yin ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Synergistic Effects ◽  
Peripheral Nerve Regeneration ◽  
Mimetic Peptide ◽  
Peptide Epitopes ◽  
Self Assembling ◽  
Peptide Hydrogels

We developed the functionalized self-assembling peptide nanofiber hydrogel RAD/KLT/RGI that was dual-functionalized with VEGF- and BDNF-mimetic peptide epitopes for peripheral nerve regeneration.

Improved Peripheral Nerve Regeneration in Streptozotocin-Induced Diabetic Rats by Oral Lumbrokinase

2015 ◽  
Vol 43 (02) ◽  
pp. 215-230 ◽  
Author(s):  
Han-Chung Lee ◽  
Yuan-Man Hsu ◽  
Chin-Chuan Tsai ◽  
Cherng-Jyh Ke ◽  
Chun-Hsu Yao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Transforming Growth Factor ◽  
Peripheral Nerve Regeneration ◽  
Interleukin 1 ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Nerve Lesion

We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I–II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery.

SMP-534 inhibits TGF-β-induced ECM production in fibroblast cells and reduces mesangial matrix accumulation in experimental glomerulonephritis

2005 ◽  
Vol 289 (5) ◽  
pp. F998-F1004 ◽  
Author(s):  
Eiji Sugaru ◽  
Mutsuko Sakai ◽  
Kazuhiko Horigome ◽  
Teruhisa Tokunaga ◽  
Makoto Kitoh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Periodic Acid ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Cortical Region ◽  
Fibroblast Cells ◽  
Periodic Acid Schiff ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Transforming growth factor-β (TGF-β) is a potent fibrotic factor responsible for the synthesis of extracellular matrix (ECM) and is implicated as the major determinant in pathogenesis of chronic fibroses, including kidney. The novel small compound SMP-534 reduced ECM production induced by TGF-β in fibroblast cells. SMP-534 inhibited TGF-β-induced p38 mitogen-activated protein kinase (p38) activation but did not inhibit epidermal growth factor (EGF)-induced extracellular signal-related kinase (ERK) activation. We also found that oral administration of SMP-534 dose dependently lowered hydroxyproline contents in the cortical region of the kidney in rat anti-Thy-1 nephritis models. In periodic acid-Schiff staining of kidney sections, ECM accumulation was reduced by SMP-534 treatment. These data indicate that SMP-534 has potential in therapy for fibrotic diseases, including nephropathy.

scholarly journals Cell signaling abnormalities in cardiomyopathy caused by lamin A/C gene mutations

2017 ◽  
Vol 46 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Howard J. Worman
Keyword(s):  
Cell Signaling ◽  
Transforming Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Gene Mutations ◽  
Transforming Growth Factor Β ◽  
Lamin A ◽  
Preclinical Research ◽  
Intermediate Filament Proteins ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Mutations in the lamin A/C gene (LMNA) encoding intermediate filament proteins associated with the inner nuclear membrane cause diseases known as laminopathies. Most LMNA mutations cause dilated cardiomyopathy with variable skeletal muscular dystrophy. Cell signaling abnormalities have been discovered in hearts of mouse models of cardiomyopathy caused by LMNA mutations that contribute to pathogenesis. These include abnormally increased signaling by extracellular signal-regulated kinase 1 and kinase 2 and other mitogen-activated protein kinases, protein kinase B/mammalian target of rapamycin complex 1 and transforming growth factor-β. Preclinical research suggests that specific inhibitors of these abnormally activated cell signaling pathways may be useful in treating human patients with this disease.

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