Granulocyte colony-stimulating factor improves neurological function and angiogenesis in intracerebral hemorrhage rats
Authors: Y-Y Zhuang
S-D Liang
Z-Y Gao
L-Q Ma
Y-Z Zhao
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: G-CSF; PI3K/AKT signaling pathway; angiogenesis; neural protection; intracerebral hemorrhage
Affiliations: Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, China. .

Abstract:  Objective: Granulocyte colony-stimulating factor (G-CSF) plays a role in regulating phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/AKT) pathway, affecting cell proliferation and apoptosis, and inducing vascular endothelial growth factor (VEGF) expression. This study investigated the mechanism of G-CSF on angiogenesis and neural protection after intracerebral hemorrhage (ICH). Materials and methods: The rats were divided into four groups, including sham, ICH, ICH+G-CSF, and ICH+G-CSF+LY294002 (PI3K/AKT signaling pathway specific inhibitor). Cerebral neurological dysfunction was tested by Garcia scoring. Cell apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Angiogenesis marker CD34 expression, PI3K/AKT signaling pathway, B-cell lymphoma-2 (Bcl-2), and VEGF expressions were compared by IHC. Rat cerebral nerve RN-c cells were divided into four groups, including control, oxygen-glucose deprivation (OGD), OGD+G-CSF, and OGD+G-CSF+LY294002. Results: Neurological dysfunction was more evident; CD34+ cell number, VEGF expression, and cell apoptosis significantly increased; phosphorylated AKT (p-AKT) and Bcl-2 levels markedly reduced in ICH group compared with sham group. G-CSF apparently up-regulated p-AKT and Bcl-2 expressions, attenuated cell apoptosis, and elevated CD34+ cell number. LY294002 significantly decreased p-AKT, Bcl-2, and VEGF expressions, and alleviated the cell apoptosis protective and angiogenesis effect induced by G-CSF. OGD treatment induced RN-c cell apoptosis, down-regulated p-AKT and Bcl-2 expressions, and enhanced the tube capacity of vascular endothelial cells (VEC). G-CSF markedly elevated p-AKT and Bcl-2 contents in RN-c cells, declined cell apoptosis, increased p-AKT and VEGF levels in VEC, and enhanced tube capacity. Conclusions: G-CSF enhanced PI3K/AKT signaling pathway activity, promoted Bcl-2 and VEGF expression, reduced nerve cell apoptosis, and enhanced tube capacity of VECs, which may be the mechanism of G-CSF in improving neurological function and angiogenesis after ICH. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a large set of papers (n=190 as of today and growing) that share a very similar layout. Subsets of these papers appear to share similar Kaplan-Meier survival plots, correlation plots, flow cytometry panels, and overlapping photos of wound-healing, transwell assays, etc. Yet, there is little to no overlap between the authors of these papers or their departments and affiliated institutions. I have been calling this set the  Comb papers, because the Kaplan-Meier plots have a comb-like appearance. For PubPeer user Hoya Camphorifolia, the survival plots look like Lego blocks. Many of these survival plots show a sudden drop of survival at 75 months. Another characteristic is the lack of percentages in their Tables I, in columns labeled with percentages, and the nicely even spread of patients into roughly equally-sized group, no matter which parameter is chosen. The very similar layout and overlapping photos suggest these papers might have all been created by the same entity, perhaps a paper mill. Here is Figure 1C from this paper, showing the Comb- (or Lego-)like survival plot with its nosedive at 75 months.  , 
 Fig 3G.  A negative correlation between relative levels of miR-4262 and KLF6 in esophageal cancer tissues .  At right, a superimposition of three versions of the same scatterplot, in other papers - using different colors, so that the data-points used in all three variants are a dark greenish-brown. Surprisingly many of those points are also visible in Fig 3G, suggesting that it emerged from the same basis table of coordinates. Here adding 3G to the superimposition:  ,