Spatiotemporal expression of Ski after rat spinal cord injury

Zhou, Kaisheng; Wu, Nan; Feng, Dongliang; Yi, Zhigang; Zhu, Yandong; Long, Zai-Yun; Li, Sen; Zhang, Haihong; Wu, Yamin

doi:10.1097/wnr.0000000000000729

Cited by 18 publications

(5 citation statements)

References 35 publications

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“… 167 In rats with a spinal cord injury, Ski is upregulated in reactive astrocytes, but not in neurons. 187 The inhibition of Smad1 and Smad2 by Ski induces the expression of some neural markers; 188 whereas, Ski -KO mice exhibit reduced expression of nestin, an intermediate filament protein of neuroepithelial cells and myocytes precursors; 189 , 190 embryos of Ski -KO mice also exhibit extra vestigial-digits. 190 Ski appears to maintain the identity of callosal neurons in the developing neurocortex by blocking Ctip2 gene expression through a Ski/Stab2/HDAC1 complex.…”

Section: Role Of Ski and Snon In Development And Tissue Homeostasismentioning

confidence: 99%

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Tecalco-Cruz

Ríos-López

Vázquez‐Victorio

et al. 2018

Sig Transduct Target Ther

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The transforming growth factor-β (TGF-β) family plays major pleiotropic roles by regulating many physiological processes in development and tissue homeostasis. The TGF-β signaling pathway outcome relies on the control of the spatial and temporal expression of >500 genes, which depend on the functions of the Smad protein along with those of diverse modulators of this signaling pathway, such as transcriptional factors and cofactors. Ski (Sloan-Kettering Institute) and SnoN (Ski novel) are Smad-interacting proteins that negatively regulate the TGF-β signaling pathway by disrupting the formation of R-Smad/Smad4 complexes, as well as by inhibiting Smad association with the p300/CBP coactivators. The Ski and SnoN transcriptional cofactors recruit diverse corepressors and histone deacetylases to repress gene transcription. The TGF-β/Smad pathway and coregulators Ski and SnoN clearly regulate each other through several positive and negative feedback mechanisms. Thus, these cross-regulatory processes finely modify the TGF-β signaling outcome as they control the magnitude and duration of the TGF-β signals. As a result, any alteration in these regulatory mechanisms may lead to disease development. Therefore, the design of targeted therapies to exert tight control of the levels of negative modulators of the TGF-β pathway, such as Ski and SnoN, is critical to restore cell homeostasis under the specific pathological conditions in which these cofactors are deregulated, such as fibrosis and cancer.

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Section: Role Of Ski and Snon In Development And Tissue Homeostasismentioning

confidence: 99%

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Tecalco-Cruz

Ríos-López

Vázquez‐Victorio

et al. 2018

Sig Transduct Target Ther

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“…These studies have demonstrated that Ski also plays an important role in the physiological and pathological processes of the central nervous system. In a previous study by our group, we found that Ski was signi cantly upregulated after spinal cord injury and showed a signi cant positive correlation with the expression of the astrocyte-speci c molecule Gfap [32], which suggests that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. In further in vitro experiments, it was found that intervention of Ski expression by lentiviral knockdown and overexpression could signi cantly affect the proliferation and migration of activated astrocytes [33][34][35][36].…”

Section: Introductionmentioning

confidence: 67%

“…In the course of subsequent studies, researchers also found that Ski plays a key role in regulating the activation and proliferation of broblasts as well as broma cells [50][51][52]. In a previous study by our group, we found that Ski was signi cantly upregulated in rat spinal cord and activated astrocytes after spinal cord injury [32]. In vitro, intervention of Ski expression by knockdown and overexpression can signi cantly affect the proliferation and migration of astrocytes [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Lentivirus-mediated knockdown of Ski inhibits glial scar formation and promotes axonal regeneration and functional recovery after spinal cord injury in rats

Wang

Ran

et al. 2023

Preprint

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The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and functional recovery after spinal cord injury, we prepared a rat spinal cord injury model using Allen's percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly inhibited the expression of Glial Fibrillary Acidic Protein (Gfap) and Vimentin, the hallmark molecules of glial scar, and increased the expression of Neurofilament-200 (Nf-200), a key molecule for axonal regeneration, and Synaptophysin, a key molecule for synapse formation. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results demonstrate that Ski is an important regulator of glial scar formation at the injury site and promotes axonal regeneration and synapse formation after spinal cord injury, and is a potential target for targeted therapy after spinal cord injury.

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“…18 Furthermore, Ski has been implicated to involve in many cellular process. 19 Our previous studies have demonstrated that Ski was strikingly up-regulated in reactive astrocytes after spinal cord injury in vivo, 20 and knockdown of Ski arrested astrocytes' cell cycle process and decreased cell proliferation in vitro. 21 However, the accurate mechanism of Ski regulating astrogliosis remains further to be elucidated.…”

Section: Introductionmentioning

confidence: 97%

Knockdown of Ski decreased the reactive astrocytes proliferation in vitro induced by oxygen‐glucose deprivation/reoxygenation

Zhao

Zhou

et al. 2018

J of Cellular Biochemistry

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Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury. However, its role in the process of reactive astrogliosis after cerebral ischemia and its definite mechanism still remains unknown. This study is to elucidate the role of Ski in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. The expression of Ski was proved to be up-regulated in OGD/R model. Meanwhile, Up-regulation of Ski was accompanied with high ratio of EdU (+) cells and up-expression of related proteins including GFAP, PCNA, CDK4, and CyclinD1, which demonstrated the distinct activation and proliferation of astrocytes after stimulation by OGD/R. Astrocytes were transfected with Ski-specific siRNA to knockdown Ski expression and subsequently attenuated OGD-induced astrocyte proliferation. Our results also showed that Ski down-regulation could suppress the activity of the Ras-Raf-ERK1/2 signaling pathway. Together, knockdown of Ski can effectively inhibit the proliferation of reactive astrogliosis via suppressing the Ras-Raf-ERK1/2 pathway. These findings indicated that maybe Ski is a promising therapeutic target for cerebral ischemic injury.

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Spatiotemporal expression of Ski after rat spinal cord injury

Cited by 18 publications

References 35 publications

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease

Lentivirus-mediated knockdown of Ski inhibits glial scar formation and promotes axonal regeneration and functional recovery after spinal cord injury in rats

Knockdown of Ski decreased the reactive astrocytes proliferation in vitro induced by oxygen‐glucose deprivation/reoxygenation

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