Progress in experimental research on SPRED protein family

Gong, Jian; Yan, Zhangren; Liu, Qiao

doi:10.1177/0300060520929170

Cited by 7 publications

(5 citation statements)

References 69 publications

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“…Specific cytokine/chemokines such as SPRED2 , OSM and IL1A (at all three time-points), and CXCL6 (at 3 h post-IS) were up-regulated in participants with poor outcome, while FLT3LG and CCR7 (at all three time-points) were down-regulated. SPRED proteins modulate angiogenesis, vascular repair, and autophagy [ 41 , 42 ]. Thrombin aggravates astrocyte injury following IS by SPRED2 activation of autophagy pathways [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes

Amini

Knepp

Rodríguez

et al. 2023

J Neuroinflammation

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Background This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes. Methods Peripheral blood samples from the CLEAR trial IS patients at ≤ 3 h, 5 h, and 24 h after stroke were compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome assessed using the modified Rankin Scale (mRS) and the NIH Stroke Scale (NIHSS). Results The expression of 467, 526, and 571 genes measured at ≤ 3, 5 and 24 h after IS, respectively, were associated with poor 90-day mRS outcome (mRS ≥ 3), while 49, 100 and 35 genes at ≤ 3, 5 and 24 h after IS were associated with good mRS 90-day outcome (mRS ≤ 2). Poor outcomes were associated with up-regulated genes or pathways such as IL-6, IL-7, IL-1, STAT3, S100A12, acute phase response, P38/MAPK, FGF, TGFA, MMP9, NF-kB, Toll-like receptor, iNOS, and PI3K/AKT. There were 94 probe sets shared for poor outcomes vs. controls at all three time-points that correlated with 90-day mRS; 13 probe sets were shared for good outcomes vs. controls at all three time-points; and 46 probe sets were shared for poor vs. good outcomes at all three time-points that correlated with 90-day mRS. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome for mRS and NIHSS. Poor outcome modules were enriched with up-regulated neutrophil genes and with down-regulated T cell, B cell and monocyte-specific genes; and good outcome modules were associated with erythroblasts and megakaryocytes. Finally, genes identified by genome-wide association studies (GWAS) to contain significant stroke risk loci or loci associated with stroke outcome including ATP2B, GRK5, SH3PXD2A, CENPQ, HOXC4, HDAC9, BNC2, PTPN11, PIK3CG, CDK6, and PDE4DIP were significantly differentially expressed as a function of stroke outcome in the current study. Conclusions This study suggests the immune response after stroke may impact functional outcomes and that some of the early post-stroke gene expression markers associated with outcome could be useful for predicting outcomes and could be targets for improving outcomes.

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Section: Discussionmentioning

confidence: 99%

Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes

Amini

Knepp

Rodríguez

et al. 2023

J Neuroinflammation

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“…While activation of p38 MAPK is associated with stress-induced erythropoiesis [ 35 ], ERK1 serves as a negative regulator of the steady-state splenic erythropoiesis [ 36 ] operating not through the EPO/EPOR signaling pathway but involving the Sonic Hedgehog/BMP4 pathway [ 37 , 38 ]. There are many negative regulators involved in the MAPK pathway including the Spred 1 protein, Raf kinase inhibitor protein RKIP, p38 MAPKs and JNKs downregulator DUSP1/MKP1 [ 39 , 40 , 41 ]. Cytoplasmic ERK1/2 can shape also a negative feedback regulatory mechanism upstream of the ERK pathway by phosphorylation of protein kinases SOS, Raf-1, and MEK [ 42 ].…”

Section: Epor/mapk and Erythropoiesismentioning

confidence: 99%

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Tóthová

Šemeláková

Solárová

et al. 2021

IJMS

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Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.

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“…Specific cytokine/chemokines such as SPRED2 , OSM and IL1A (at all three time points), and CXCL6 (at 3h post IS) were up-regulated in subjects with poor outcome, while FLT3LG and CCR7 (at all three time points) were down-regulated. SPRED proteins modulate angiogenesis, vascular repair [64] and autophagy [65]. Thrombin aggravates astrocyte injury following IS by SPRED2 activation of autophagy pathways [65].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Gene Expression at 3 to 24 Hours Correlates with and Predicts 90-Day Outcome Following Human Ischemic Stroke

Amini

Knepp

Rodríguez

et al. 2022

Preprint

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This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes and an early gene profile that predicted 90-day outcomes. Peripheral blood from the CLEAR trial IS patients was compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome (NIHSS-NIH Stroke Scale, mRS-modified Rankin Scale). The expression of 467, 526, and 571 genes measured at ≤3, 5 and 24 hours after IS, respectively, were associated with poor 90-day mRS outcome (mRS=3-6), while 49, 100 and 35 associated with good mRS 90-day outcome (mRS=0-2). Poor outcomes were associated with up-regulated MMP9, S100A12, interleukin-related and STAT3 pathways. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome. Poor outcome modules were enriched in down-regulated T cell and monocyte-specific genes plus up-regulated neutrophil genes and good outcome modules were associated with erythroblasts and megakaryocytes. Using the difference in gene expression between 3 and 24 hours, 10 genes correctly predicted 100% of patients with Good 90-day mRS outcome and 67% with Poor mRS outcome (AUC=0.88) in a validation set. The predictors included AVPR1A, which mediates platelet aggregation, release of coagulation factors and exacerbates the brain inflammatory response; and KCNK1 (TWIK-1), a member of a two-pore potassium channel family, which like other potassium channels likely modulates stroke outcomes. This study suggests the immune response after stroke impacts long-term functional outcomes. Furthermore, early post-stroke gene expression may predict stroke outcomes and outcome-associated genes could be targets for improving outcomes.

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Progress in experimental research on SPRED protein family

Cited by 7 publications

References 69 publications

Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes

Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes

The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Peripheral Blood Gene Expression at 3 to 24 Hours Correlates with and Predicts 90-Day Outcome Following Human Ischemic Stroke

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