Clinical significance of CTGF and Cry61 protein in extraocular muscles of strabismic patients.

PURPOSE: To investigate the relationship between clinical features and protein amounts of Cysteine-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2), which are vital components and regulators of the extracellular matrix in resected muscles from strabismus surgery. METHODS: Strabismus patients who were diagnosed with horizontal concomitant strabismus or inferior oblique overaction (IOOA) and required extraocular muscles (EOMs) resection to correct eye position were included in this study. The protein amounts were measured by enzyme-linked immunosorbent assay (ELISA) in resected EOMs. Multivariable linear regression was used to investigate the associations, adjusting for gender, age (continuous), amblyopia, and disease duration. RESULTS: A total of 141 muscles (including 38 lateral, 81 medial rectus, and 22 inferior oblique muscles) from 128 patients were collected in this study. The amount of Cry61 and CTGF per millimeter was significantly negatively associated with deviation angle in intermittent exotropia patients (Cry61: ß, - 1.44; 95%CI, - 2.79 to - 0.10, p = 0.035; CTGF: ß, - 3.14; 95%CI, - 5.06 to - 1.22, p = 0.002). The same relationship was also detected in the partially accommodative and non-accommodative esotropia patients, although it was not statistically significant (Cry61: ß, - 2.40; 95%CI, - 5.05 to 0.24; p = 0.073; CTGF: ß, - 3.47; 95%CI, - 9.18 to 2.87; p = 0.269). The amount of Cry61 and CTGF per millimeter showed significant associations with the degree of IOOA (p < 0.05). CONCLUSIONS: Taken together, our results demonstrated a significant relationship between deviation angle and protein amount of Cry61 and CTGF and implied that Cry61 and CTGF may play important roles in modulation of EOM contractility, which provide new insights into strabismus pathogenesis.

Cysteine-rich 61(CYR61) alleviates cyclophosphamide-induced proliferation inhibition in ovarian granulosa cells via suppressing NLRP3/caspase1-mediated pyroptosis.

BACKGROUND: We investigated the level of Cysteine-rich 61 (CYR61) in premature ovarian failure as well as its regulatory molecular mechanism in this study. METHODS AND RESULTS: Cyclophosphamide (CTX) was used to induce OGCs (rat ovarian granulosa cells) and rats to establish in vivo and in vitro premature ovarian failure models. H&E staining was used to detect the pathological changes of ovarian histopathology. Si-NLRP3 (NOD-like receptor thermal protein domain associated protein 3, NLRP3) and si-CYR61 were transfected into OGCs using lipofectamine 3000. RT-qPCR and western blot were used to detect the expressions of CYR61 in ovarian tissue and OGCs. It showed that the expression of CYR61 was significantly down-regulated in premature ovarian failure model. Cell viability was detected using a Cell Counting Kit-8 (CCK-8) kit. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling) staining was used to detect the apoptosis. 5-Ethynyl-2'-deoxyuridine (EdU) and SA-ß-gal (senescence-associated ß-galactosidase) staining were used to assess the proliferation and senescence. The expression of CYR61 in OGCs and ovarian tissues were detected by immunofluorescence and immunohistochemical staining. Overexpression of CYR61 significantly promoted OGCs proliferation and inhibited pyroptosis and apoptosis. Western blot was used to detect the protein expressions of p53 and p21 in OGCs. Flow cytometry was used to detect the pyroptosis. CYR61 overexpression inhibited the expression of NLRP3 and caspase-1 in CTX-induced OGCs according to western blot results. Moreover, we found that CYR61 overexpression down-regulated the protein expressions of p53 and p21 in CTX-induced OGCs. CONCLUSION: CYR61 inhibited CTX-induced OGCs senescence, and the mechanism may be related to the regulation of caspase-1/NLRP3-induced pyroptosis.

Diagnostic value of cysteine rich 61, glyoxalase Ⅰ and microRNA-155 in endometrial carcinoma / 中国医师进修杂志

Objective:To investigate the diagnostic value of cysteine rich 61 (Cyr61), glyoxalase Ⅰ (GLO -1) and microRNA-155(miR-155) in endometrial carcinoma.Methods:Eighty-five patients with endometrial cancer treated in Lu Southwest Hospital from June 2017 to March 2020 were selected as the observation group, including 15 cases of recurrence and 70 cases of non-recurrence. In addition, 85 patients with benign uterine lesions were selected as the control group. The levels of serum Cyr61, GLO-1 and miR-155 were compared between the two groups, the correlation between the levels of serum Cyr61, GLO-1 and miR-155 and clinicopathological features were analyzed, the receiver operating characteristic (ROC) curve was drawn, the diagnostic value of the levels of serum Cyr61, GLO-1 and miR-155 in endometrial cancer were evaluated, and the relationship between the levels of serum Cyr61, GLO-1 and miR-155 and the recurrence of endometrial cancer were analyzed.Results:The levels of serum Cyr61, GLO-1 and miR-155 in the observation group were higher than those in the control group: (294.74 ± 78.41) μg/L vs. (156.82 ± 50.62) μg/L, (96.27 ± 19.85) pmol/L vs. (79.83 ± 15.69) pmol/L, 6.82 ± 2.27 vs. 2.57 ± 0.78, the differences were statistically significant ( P<0.05). The levels of serum Cyr61, GLO-1 and miR-155 in patients with endometrial cancer were positively correlated with clinical stage, myometrial invasion and lymph node metastasis ( P<0.05). The area under the curve(AUC) of serum Cyr61, GLO-1 and miR-155 in the combined diagnosis of endometrial cancer was 0.906. The levels of serum Cyr61, GLO-1 and miR-155 in recurrence patients were higher than those non-recurrence patients : (358.21 ± 89.63) μg/L vs. (281.14 ± 75.29) μg/L, (109.89 ± 20.14) pmol/L vs. (93.35 ± 16.37)pmol/L, 8.04 ± 2.51 vs. 6.56 ± 2.17, the differences were statistically significant ( P<0.05). The levels of serum Cyr61, GLO-1 and miR-155 were the risk factors of recurrence in patients with endometrial cancer ( P< 0.05). Conclusions:The levels of serum Cyr61, GLO-1 and miR-155 in patients with endometrial cancer are significantly increased, which are related to clinical stage, degree of invasion, lymph node metastasis and recurrence. Detecting their levels can be used to diagnose endometrial cancer and predict recurrence, so as to guide clinical treatment.

Cysteine-rich 61 (Cyr61) upregulated in pulmonary arterial hypertension promotes the proliferation of pulmonary artery smooth muscle cells.

Background: We aimed to evaluate the expression of cysteine rich 61 (Cyr61) in patients with pulmonary arterial hypertension (PAH) as well as monocrotaline (MCT) induced PAH rat, and further investigate the effects and potential mechanisms of Cyr61 on the proliferation of pulmonary arterial smooth muscle cells (PASMCs). Methods and Results: Plasma samples were collected from 20 patients with idiopathic PAH, 20 connective tissue disease (CTD) associated PAH, 29 age-, gender- and disease matched CTD without PAH patients, and 28 healthy controls. ELISA was used to detect the level of Cyr61 in plasma. MCT-induced PAH (MCT-PAH) rat model was established by a single subcutaneous injection of MCT (60mg·kg-1). Lung tissues and pulmonary arteries of rats were collected, while the PASMCs were dissected and cultivated for in vitro experiments. Expression of Cyr61 in the lung tissues, pulmonary arteries and PASMCs were tested by immunohistochemical staining, western blot and quantitative real-time polymerase chain reaction. PASMCs from PAH rats were stimulated by exogenous recombinant Cyr61 protein and knocked down by small interfering RNA. Cell Counting Kit-8 assay was used to identify cell proliferation and the expression of p-AKT and AKT were analysed by western blot. The results showed plasma level of Cyr61 in PAH patients, especially CTD-PAH patients, were significant higher than that of CTD without PAH patients and healthy controls. Compared with wild rats, Cyr61 was overexpressed in the lung tissue, pulmonary arterial and PASMCs in PAH rats. Exogenous recombinant Cyr61 protein promoted the proliferation of PASMCs in a dose-dependent manner. While the expression of Cyr61 in PASMCs was inhibited by specific siRNA, cell proliferation was restrained and the expression of p-AKT declined. Conclusion: Plasma Cyr61 concentration in PAH patients was highly increased. Cyr61 could promote PASMCs proliferation via AKT pathway, indicating that Cyr61 may play a role in the pathogenesis of PAH.

The profile of Cyr61 expression data correlate to the skin inflammation in psoriasis.

The data presented in this article are related to the research article entitled "Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway" (Pinru Wu, Gang Ma, Xianjin Zhu, Ting Gu, Jie Zhang, Yue Sun, Hui Xu, Rongfen Huo, Beiqing Wang, Baihua Shen, Xiangdong Chen, Ningli Li, 2016) [1]. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. In this dataset skin samples from normal donors and psoriasis vulgaris patients were examined the expression of Cyr61 and IL-8 using immunohistochemistry. IMQ-induced psoriasis-like mice were treated with anti-Cyr61monoclonal antibodies (mAb).

The expression and significance of cysteine-rich 61, connective tissue growth factor, vascular endothelial growth factor and microvascular density marked by CD105 in muscle tissue of patients with dermatomyosits and polymyosits / 中华风湿病学杂志

Objective By detecting vascular cysteine-rich 61(Cyr61) related factor,connective tissue growth factor (CTGF),vascular endothelial growth factor (VEGF) and CD105 markers of microvascular density (MVD) of muscle tissue in patients with PM/DM,the role and significance of the expression of Cyr61,CTGF,VEGF and CD105 in the process of vascular lesions of dermatomyosits (DM) and polymyosits (PM) were discussed.Methods The expression of Cyr61,CTGF,VEGF and CD105 markers of micro vascular density (MVD) were detected in 10 cases of DM,10 cases of PM and 20 controls by using immunohistochemical Envision two step method.Data were analyzed using Statistical Product and Service Solutions (SPSS) statistical software.Fisher's exact probability analysis and Spearman correlation analysis were conducted.Results Compared with the control group,Cyr61,CTGF,VEGF positive expression rate in muscle tissue of patients with DM and PM group were significantly different (P＜0.01),the positive expression rates of Cyr61,CTGF,VEGF in DM group and PM group were 90％,70％,90％,80％,80％,70％,and the control group (5％,10％,5％) respectively.In the muscle tissue of patients with DM and PM group,CD105 markers of capillaries could be seen,and MVD in DM and PM group were higher than that in the control group,the difference was statistically significant (F=8.103,P=0.001).Cyr61,CTGF and VEGF protein expression levels in muscle tissueof patients with DM and PM were positively correlated with MVD.Conclusion The muscle tissue of PM/DMpatients may have new blood vessels formation.Cyr61,CTGF,VEGF may be involved in the formation of newblood vessels in the PM/DM muscle tissue.The results of this study suggest that microvascular lesion plays animportant role in the immune pathogenesis of inflammatory myopathy such as PM/DM.

Prognostic significance of expression of cysteine-rich 61 and cyclooxygenase-2 in gastric cancer.

BACKGROUND: This study aimed to evaluate the clinical significance of cysteine-rich 61 (Cyr-61/CCN1) and cyclooxygenase-2 (COX-2), and further explored their combined prognostic significance in gastric cancer. METHODS: This retrospective study examined the expressions of Cyr-61 and COX-2 in 82 surgically removed gastric cancer specimens and 43 non-tumor gastric mucosa specimens by immunohistochemical staining to identify the abnormal expression of Cyr-61 or COX-2 in gastric cancer. Crude survival curves were constructed by the Kaplan-Meier method and Cox proportional hazards regression analysis was performed to confirm the prognostic roles of Cyr-61/COX-2 as well as sex and histological grade. RESULTS: The expressions of Cyr-61 (p < 0.001) and COX-2 (p = 0.001) were both significantly up-regulated in gastric cancer samples compared with non-tumor gastric mucosa samples. The high expression of Cyr-61 or COX-2 was associated with invasion, lymph node metastasis, distant metastases, poor histological differentiation, advanced TNM stage and lower 5-year survival rate (all p < 0.05). Both Cyr-61 and COX-2 high expressions [hazard ratio (HR) = 31.8, 95 % confidence interval (CI) 4.09-246.8] was associated the higher risk of death during 5 years follow up than single Cyr-61 high expression (HR = 4.1, 95 % CI 1.5-11.6) or COX-2 high expression (HR = 2.9, 95 % CI 1.06-7.8). CONCLUSIONS: Cyr-61 and COX-2 expressions are associated with the progression of gastric cancer. Additionally, combined expressions of Cyr-61 and COX-2 has a higher prognostic value than single expression.

Systemic overexpression of matricellular protein CCN1 exacerbates obliterative bronchiolitis in mouse tracheal allografts.

Obliterative bronchiolitis (OB) involves airway epithelial detachment, fibroproliferation, and inflammation, resulting in chronic rejection and transplant failure. Cysteine-rich 61 (CCN1) is an integrin receptor antagonist with a context-dependent role in inflammatory and fibroproliferative processes. We used a mouse tracheal OB model to investigate the role of CCN1 in the development of lung allograft OB. C57Bl/6 mice received a systemic injection of CCN1-expressing adenoviral vectors 2 days prior to subcutaneous implantation of tracheal allografts from major MHC-mismatched BALB/c mice. We treated another group of tracheal allograft recipients with cyclic arginine-glycine-aspartic acid peptide to dissect the role of αvß3-integrin signaling in mediating CCN1 effects in tracheal allografts. Allografts were removed 4 weeks after transplantation and analyzed for luminal occlusion, inflammation, and vasculogenesis. CCN1 overexpression induced luminal occlusion (P < 0.05), fibroproliferation, and smooth muscle cell proliferation (P < 0.05). Selective activation of αvß3-integrin receptor failed to mimic the actions of CCN1, and blocking failed to inhibit the effects of CCN1 in tracheal allografts. In conclusion, CCN1 exacerbates tracheal OB by enhancing fibroproliferation via an αvß3-integrin-independent pathway. Further experiments are required to uncover its potentially harmful role in the development of OB after lung transplantation.

The mechanism of CCN1-enhanced retinal neovascularization in oxygen-induced retinopathy through PI3K/Akt-VEGF signaling pathway.

BACKGROUND: CCN1 (also called Cyr 61) is an extracellular matrix signaling molecule that has been implicated in neovascularization through its interactions with several endothelial integrin receptors. The roles of vascular endothelial growth factor (VEGF) in angiogenesis are well described. The aim of this study was to investigate the signal transduction mechanism of CCN1-PI3K/Akt-VEGF in retinopathy of prematurity (ROP), and the effects of CCN1 knockdown on ROP. METHODS: The oxygen-induced retinopathy (OIR) model was established in C57BL/6J mice exposed to a high concentration of oxygen. Retinas were obtained from the normoxia, OIR, OIR control (treated with scramble siRNA) and OIR treated (with CCN1 siRNA) groups. Retinal neovascularization (RNV) was qualitatively analyzed with ADPase staining and quantitatively analyzed by counting neovascular endothelial cell nuclei at postnatal day 17 when RNV reached a peak. mRNA level and protein expression of CCN1, p-Akt, and VEGF were measured by real-time PCR and Western blotting, and located with immunohistochemistry. RESULTS: CCN1 depletion resulted in less neovascularization clock hour scores in the number of preretinal neovascular cells compared with the OIR treated group (1.28±0.83 versus 4.80±0.82; and 7.12±2.50 versus 23.25±2.35, respectively, both P<0.05). Furthermore, CCN1, p-Akt and VEGF mRNA, and protein were significantly expressed in the retina of the OIR and OIR control groups. Intravitreal injection of CCN1 siRNA significantly reduced PI3K/Akt-VEGF pathway expression of the OIR mouse model (all P<0.05). CCN1 siRNA significantly enhanced the avascular area and avascular diameter of OIR model (P<0.05). CCN1 siRNA decreased the levels of IL-1ß, IL-6, and TNF-α significantly compared to the OIR group (P<0.05). CONCLUSION: These results suggest that CCN1 plays an important role in RNV via the PI3K/Akt-VEGF signaling pathway. CCN1 may be a potential target for the prevention and treatment of ROP.

The protection effect of cysteine rich-protein 61 on renal tubular epithelial cells against apoptosis induced by hypoxia / 中华肾脏病杂志

Objective To observe the expression of cysteine rich-protein 61 (Cyr61) on renal tubular cells,to explore its effects against hypoxic induced kidney injury and the underlying mechanisms.Methods A stably Cyr61 expressed tubular cell line Cyr61-HK2 was established based on HK2 cells and recombinant Cyr61-lentivirus.BrdU incorporation assay was used for cell proliferation.The apoptosis of cells was analyzed by flow cytometry with Annexin V and propidiumiodide staining.Western bloting was used to detect the protein expression of BAD,Akt and ERK.Results (1) Cyr61-HK2 cells displayed more proliferation ability than HK2 cells.(2) Under hypoxia condition,the apoptosis of both HK2 and Cyr61-HK2 cells increased,but the apoptosis of Cyr61-HK2 cells was lesser than HK2 cells.(3) The expression of Cyr61 led to the phosphorylation of BAD,Akt and ERK on 0 h,0.5 h,1 h (all P ＜ 0.05).Conclusion The expression of Cyr61 can promote cell proliferation and dampen cell apoptosis induced by hypoxia,which may be involved in the Akt/ERK signal pathway.

Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανß3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.

Diabetes causes a number of metabolic and physiological abnormalities in the retina. Many of the molecular and physiological abnormalities that develop during diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 (MCP-1) is an important factor involved in diabetic retinopathy. In a previous study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, also plays an important role in diabetic retinopathy. In addition to the direct effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. However, the mechanism through which this occurs is not completely understood in chorioretinal vascular endothelial cells. We therefore investigated the effects of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανß3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays revealed that the above inhibitors suppressed the activation of NF-κB. Additionally, deletion of the NF-κB-binding element in the MCP-1 gene promoter led to a decrease in expression in luciferase reporter assays. These results show that the induction of MCP-1 by Cyr61 is mediated through the activation of the integrin ανß3, FAK, PI3K/Akt, and IKK/NF-κB pathways in chorioretinal vascular endothelial cells.

Expression and significance of CCN1 in oxygen-induced retinal neovascularization of mice / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To explore the expression and significance of cysteine- rich 61 ( CCN1/Cyr61 ) in oxygen - induced retinal neovascularization ( RNV) of mice and study the inhibition effect of CCN1 specific siRNA on RNV. METHODS:Two hundred healthy C57BL/6J mice were chosen and randomly divided into control group, hyperxia group, hyperxia control group and CCN1 treated group, with 50 mice in each group. The hyperxia control group was treated with vector plasmids by intravitreal injection. The CCN1 treated group received CCN1 siRNA recombinant plasmids by intravitreal injection. Adenosine diphosphate-ase ( ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, HE staining was applied to count the number of vascular endothelial cell nuclei breaking through the internal limiting membrane, protein and mRNA level expression of CCN1 were measured by immunohistochemistry, Western blot and RT-PCR. RESULTS: There were large nonperfusion area and a large number of vascular endothelial cell nuclei breaking through the internal limiting membrane ( 25. 25 ± 1. 26;23. 12 ± 1. 16 ) in the hyperxia group and the hyperxia control group. Regions of nonperfusion and vascular endothelial cell nuclei (8. 47±1. 15) were decreased in the CCN1 treated group compared to the hyperxia group and the hyperxia control group. Compared with the control group, there were high protein and mRNA expression of CCN1 in the hyperxia group and the hyperxia control group. The expression of CCN1 protein and mRNA were decreased in the CCN1 treated group compared with the hyperxia group and hyperxia control group (all P CONCLUSlON: The abnormal expression of CCN1 has close relation with RNV. The development of RNV can be markedly inhibited by RNA interference targeting CCN1, which, we believe, will provide new molecular targets and a rationale for clinical developing new strategy for ROP therapy.

Hypoxia: a master regulator of microRNA biogenesis and activity.

Hypoxia, or low oxygen tension, is a unique environmental stress that induces global changes in a complex regulatory network of transcription factors and signaling proteins to coordinate cellular adaptations in metabolism, proliferation, DNA repair, and apoptosis. Several lines of evidence now establish microRNAs (miRNAs), which are short noncoding RNAs that regulate gene expression through posttranscriptional mechanisms, as key elements in this response to hypoxia. Oxygen deprivation induces a distinct shift in the expression of a specific group of miRNAs, termed hypoxamirs, and emerging evidence indicates that hypoxia regulates several facets of hypoxamir transcription, maturation, and function. Transcription factors such as hypoxia-inducible factor are upregulated under conditions of low oxygen availability and directly activate the transcription of a subset of hypoxamirs. Conversely, hypoxia selectively represses other hypoxamirs through less well characterized mechanisms. In addition, oxygen deprivation has been directly implicated in epigenetic modifications such as DNA demethylation that control specific miRNA transcription. Finally, hypoxia also modulates the activity of key proteins that control posttranscriptional events in the maturation and activity of miRNAs. Collectively, these findings establish hypoxia as an important proximal regulator of miRNA biogenesis and function. It will be important for future studies to address the relative contributions of transcriptional and posttranscriptional events in the regulation of specific hypoxamirs and how such miRNAs are coordinated in order to integrate into the complex hierarchical regulatory network induced by hypoxia.

Expression of cysteine rich 61 and vascular endothelial growth factor in patients with multiple myeloma and their relationship with staging and therapeutic response / 白血病·淋巴瘤

Objective To investigate the expression of cystein rich 61 (Cyr61) and vascular endothelial growth factor (VEGF) in different stages of multiple myeloma (MM) patients,evaluate their relationship with angiogenesis and prognosis,and to determine the relationship between Cyr61 and VEGF.Methods Expression of Cyr61 and VEGF in BMMNC from 31 patients with different stages of MM and 10 cases of control were detected by RT-PCR.Results Expression of Cyr61 and VEGF in patients with MM (0.3652±1.5423,0.4815±1.3423) were significantly elevated in comparison to control (0.1862±0.7542,0.2012±1.2331) (P ＜ 0.05,P ＜ 0.01).Expression of Cyr61 and VEGF in stage Ⅲ (0.4632±0.1634,0.5356± 0.2342) was significantly higher than those in stage Ⅰ and stage Ⅱ (t =2.423,2.524,P ＜ 0.05),but there was no difference between stage Ⅰ and stage Ⅱ (0.2513±0.1365,0.3064±0.2124; 0.3084±0.2254,0.3653±0.1265) (t =1.782,1.824,P ＞ 0.05).The levels of Cyr61 and VEGF were significantly decreased after chemotherapy compared to before chemotherapy (P ＜ 0.01).Expression of Cyr61 and VEGF were positively correlated (r =0.8941,P ＜ 0.01).Conclusion Cyr61 and VEGF may play roles in the angiogenesis and pathophysiology of MM.It can be used to guide treatment and estimate prognosis by monitoring Cyr61 and VEGF.

Current research on cysteine-rich 61 and their application in ocular diseases / 中华实验眼科杂志

The CCN family involves a group of six secreted proteins that specifically associate with the extracellular matrix.Cyr61 is the first cloned gene of the CCN family.CYR61 can promote cell growth,adhesion,migration,differentiation,apoptosis and extracellular matrix production.The synthesis of CYR61 is highly inducible by serum growth factors,cytokines,and environmental stresses.CYR61 can also modulate the activities of several growth factors and cytokines,including transforming growth factor-β(TGF-β),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF),bone morphogenetic proteins(BMPs)and Wnt proteins.Cyr61 is an important regulator in angiogenesis,osteogenesis,and chondrogenesis,and plays an important role in embryonic development,wound healing,tumor formation and development.It is reported that CYR61 plays a role in the course of ocular neovascular diseases.It can promote the proliferation,migration and tube formation of retinal endothelial cells in vitro.Expression of Cyr61 is upregulated in the retinas of diabetic rats and the vitreous of proliferative diabetic retinopathy (PDR)patients.CYR61 is likely to be involved in the pathogenesis of diabetic retinopathy(DR).Research progress on CYR61 in recent years is reviewed in this article.

Decreased Cyr61 under Hypoxia Induces Extravillous Trophoblasts Apoptosis and Preeclampsia / 华中科技大学学报（医学）（英德文版）

During placental development,oxygen environment is not only critical for trophoblasts migration and invasion,but also fundamental for appropriate placental perfusion.Cysteine-rich 61 (Cyr61,CCN1) was expressed in the extravillous trophoblasts (EVTs) and decreased in preeclampsia.Its regulatory properties in human first-trimester extravillous trophoblast cell line (TEV-1 cells) upon a low oxygen tension were investigated.The present study examined functional changes involved in adaptation to hypoxia of the TEV-1 cells,using cobalt chloride (CoCl2) as hypoxic mimic.It was found that hypoxia inhibited growth of TEV-1 cells and induced the increase of cell apoptosis (P＜0.05).The Cyr61 expression in human EVTs was transcriptionally induced by CoCl2.Inappropriate EVTs apoptosis has been implicated in the failure of trophoblasts to fully invade and modify the uterine environment and Cyr61 down-regulation,potentially leading to preeclampsia.

Inhibition of Hyperplasia of Vascular Smooth Muscle Cell by RNA Interference of The Plasmids of Cysteine-rich61 / 中华高血压杂志

Objective To investigate the effect of RNA interference plasmids of cysteine-rich 61(Cyr61) on hyperplasia of vascular smooth muscle cell (VSMC) in rats.Methods The plasmids containing the short hairpin RNA (shRNA) of Cyr61 were constructed.Expression of Cyr61 mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.The hyperplasia of VSMC was assessed by MTT.DNA synthesis was measured by incorporating ~3H-TDR.Plasmid construction was confirmed by DNA sequencing.Results PCyr61-shRNA transfection significantly decreased the level of mRNA and protein of Cyr61 in VSMC.The cell number,optical density and concentration of DNA in pCyr61-shRNA group were significant decreased(P

Effects of radiation on growth and CCN1 expression of mice fibroblast cell line L929 / 第三军医大学学报

Objective To observe the effects of radiation on the growth and expression of cysteine-rich 61(Cyr61/CCN1) of L929 cells and investigate the relationship between CCN1 expression and radiation injury.Methods L929 cells were cultured and divided into 2 groups,cells irradiated with 4 Gy ?-irradiation as radio-group and untreated cells as control group.The cell proliferation was measured by MTT assay and plate colony formation testing.Flow cytometry was utilized to quantify the cell cycle distribution.CCN1 expression at protein and mRNA levels were determined by immunocytochemistry(ICC) and RT-PCR respectively.Results Significant inhibition of proliferation(P