title: LRG1 promotes angiogenesis through upregulating the TGF‑β1 pathway in ischemic rat brain.
abstract: Stroke is a life-threatening disease that results in significant disability in the human population. Despite the advances in current stroke therapies, a host of patients do not benefit from the conventional treatments. Thus, more effective therapies are required. It has been previously reported that leucine‑rich‑α2‑glycoprotein 1 (LRG1) is crucial during the formation of new blood vessels in retinal diseases. However, the function of LRG1 in the brain during the neovessel growth process following ischemic stroke has not been fully elucidated and the mechanism underlying its effect on angiogenesis remains unclear. The purpose of the current study was to demonstrate whether LRG1 may promote angiogenesis through the transforming growth factor (TGF)‑β1 signaling pathway in ischemic rat brain following middle cerebral artery occlusion (MCAO). In the present study, the spatial and temporal expression of LRG1, TGF‑β1, vascular endothelial growth factor (VEGF) and angiopoietin‑2 (Ang‑2) were detected in ischemic rat brain following MCAO using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and immunohistochemistry. CD34 immunohistochemistry staining was used as an indicator of microvessel density (MVD). The RT‑qPCR and western blotting results revealed that the levels of LRG1 and TGF‑β1 mRNA and protein expression were significantly increased as early as 6 and 12 h after MCAO (P<0.05), respectively, peaked at 3 days and persisted at significantly higher level until 14 days, in comparison with the control group. Additionally, VEGF and Ang‑2 were also increased following MCAO. Furthermore, the immunohistochemistry results suggested that the MVD was increased following MCAO. In addition, the results also revealed that the percentage of LRG1‑positive cells was positively correlated with the percentage of TGF‑β1‑positive cells, and the percentage of LRG1‑positive and TGF‑β1‑positive cells had a positively correlation with the MVD. Taken together, the present study indicated that LRG1 may promote angiogenesis through upregulating the TGF‑β1 signaling pathway in ischemic rat brain following MCAO. This may provide a potential therapeutic target for the treatment of ischemic stroke.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yuejia
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Pengtian
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Wu
mesh_terms: D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D006023:Glycoproteins; C000599467:LRG1 protein, rat; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A