Effect of CLIP3 Upregulation on Astrocyte Proliferation and Subsequent Glial Scar Formation in the Rat Spinal Cord via STAT3 Pathway After Injury

Abstract

Spinal cord injury (SCI) is a devastating event resulting in neuron degeneration and permanent paralysis through inflammatory cytokine overproduction and glial scar formation. Presently, the endogenous molecular mechanisms coordinating glial scar formation in the injured spinal cord remain elusive. Signal transducer and activator of transcription 3 (STAT3) is a well-known transcription factor particularly involving in cell proliferation and inflammation in the lesion site following SCI. Meanwhile, CAP-Gly domain containing linker protein 3(CLIP3), a vital cytoplasmic protein, has been confirmed to providing an optimal conduit for intracellular signal transduction and interacting with STAT3 with mass spectrometry analysis. In this study, we aimed to identify the expression of CLIP3 in the spinal cord as well as its role in mediating astrocyte activation and glial scar formation after SCI by establishing an acute traumatic SCI model in male adult rats. Western blot analysis revealed that CLIP3 increased gradually after injury, reached a peak at day 3. The immunohistochemistry staining showed the same result in white matter. With double immunofluorescence staining, we found that CLIP3 was expressed in glial cells and significant changes of CLIP3 expression occurred in astrocytes during the pathological process. Statistical analysis demonstrated there was a correlation between the number of positive cells stained by CLIP3 and STAT3 in the spinal cord after SCI. Co-immunoprecipitation further indicated that CLIP3 interacted with STAT3 in the injured spinal cord. Taken together, our study clearly suggested that CLIP3 played an essential role in astrocyte activation, associating with the STAT3 pathway activation induced by SCI.

New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection

“…NSE expression and activity are frequently increased in neuronal and glial activation and injury, major factors implicated in neurodegenerative diseases [ 71 , 72 ]. In neuronal degeneration, glial cells regulate neuronal metabolism to support stressed neurons.…”

“…Increased NSE expression and activity may also drive metabolic changes that take place in regions away from the epicenter in injured spinal cord. Secondary insult in SCI is characterized by destruction of neuronal and glial cells that leads to the expansion of the damage and loss of function [ 72 ]. Thus, mechanisms that either promote or prevent neuronal inflammation and cell death could be investigated to find new avenues for preventing and treating neurodegenerative disorders.…”

Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

“…An earlier study reported a link between increased lactate dehydrogenase and improved intracellular NSE expression in neurotoxin-exposed cells (Thomas et al, 1991). The production and function of NSE in glial activation is enhanced, with major factors involved in neurodegenerative diseases (Chen et al, 2018;Zabel and Kirsch, 2013). PFC and hippocampus Immunohistochemical analysis showed an increase in the expression of the NSE, though not statistically significant when qualitatively examined.…”

“…Kazuma and colleagues had earlier reported that AA restored behavioural deficit in addition to depleting amyloid plaques in a mouse model of AD, and attributed their findings to decreases CNS oxidative damage mediated by AA (Murakami et al, 2011). AA has been reported to protect against apoptosis by regulating the modulation of the mitochondrial pathway of cytochrome C activities that resulted in the altered release of lactate dehydrogenase (Chen et al, 2018).…”

Gene modules and non-coding RNAs involved in pancreatic tumorigenesis through acinar ductal metaplasia

“…FRK played a role in pancreatic cancer cells migration and proliferation, and was suggested to be critical therapeutic targets of pancreatic cancer [49]. CLIP3 was shown as anti-in ammatory regulator involved in TNF-α signaling [50] and also attributed to injury recovery [51], while it was a novel target in cancer predicted in the crosstalk gene network. CECR2 functions with SMARCA1 in CERF complex (CECR2-containing remodeling factor) to regulate cell differentiation and development [52].…”