title: Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury.
abstract: Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3β and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3β and ERK1/2.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.|Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Si-Pin
authors.initials: SP
authors.lastname: Zhu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Zhou-Guang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Hong-Xue
authors.initials: HX
authors.lastname: Shi
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University, Ningbo, 315300, China.
authors.forename: Fen-Zan
authors.initials: FZ
authors.lastname: Wu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, 316021, China.
authors.forename: Songbin
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Cixi People's Hospital, Wenzhou Medical University, Ningbo, 315300, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
authors.affiliation: Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Fu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. spinexu@163.com.|Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. spinexu@163.com.
authors.forename: Hua-Zi
authors.initials: HZ
authors.lastname: Xu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. xfxj2000@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008055:Lipids; D005780:Gelatin; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ER stress; Gelatin nanostructured lipid carriers; NGF; Spinal cord injury