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Liya Pi, Chunhua Fu, Yuanquing Lu, Junmei Zhou, Marda Jorgensen, Vinayak Shenoy, Kenneth E Lipson, Edward W Scott, Andrew J Bryant
Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown...
2018: Frontiers in Physiology
Zhongyi Xu, Li Chen, Min Jiang, Qianqian Wang, Chengfeng Zhang, Leihong Flora Xiang
Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61, cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes (NHEMs) were treated with recombinant CCN1 protein. Our findings reveal that CCN1 activates melanogenesis through promoting melanosome maturation and upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1) and tyrosinase via integrin α6β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways...
March 3, 2018: Journal of Investigative Dermatology
Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
Growth factors like TGFβ and CTGF (CCN2) plays a vital role in various cellular functions. TGFβ and CTGF are overexpressed in renal fibrosis. CTGF act as profibrotic stimuli to TGFβ. CCN3 is a member of CCN family which also comprises CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3). CCN3 has been shown to antagonise CTGF. In this study, we investigated the role of CCN3 in TGFβ1-mediated signalling in human podocytes culture. This study describes the novel function of CCN3 in regulation of TGFβ1 mediated non-canonical Smad signalling in human podocytes culture...
February 28, 2018: Cellular and Molecular Biology
Zhigang Tan, Jizong Zhao, Yugang Jiang
Glioma is the most common intracranial malignant tumors, accounting for about 40% of intracranial tumors. Primary or secondary drug resistance is one of the main reasons for the failure of treatment. The oncogenic or tumor-suppressive roles of miR-634 have been revealed in different types of cancer. However, the role of miR-634 in glioma remains unknown and whether miR-634 could sensitize glioma cells to temozolomide also is unclear. Here, we aim to investigate the biological function of miR-634 and the possible mechanisms in glioma...
February 23, 2018: Cancer Medicine
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
Gargi Maity, Inamul Haque, Arnab Ghosh, Gopal Dhar, Vijayalaxmi G Gupta, Sandipto Sarkar, Imaan Azeem, Douglas McGregor, Abhishek Choudhary, Donald R Campbell, Suman Kambhampati, Sushanta K Banerjee, Snigdha Banerjee
Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model...
February 6, 2018: Journal of Biological Chemistry
Rita A Costa, Deborah M Power
Skin wound healing has been widely studied in mammalian models but the information on teleost cutaneous healing is sparse and frequently considered in the context of viral or bacterial infections or parasitic infestations in aquaculture. In the present study a detailed time course (0 h, 6 h, 1, 2, 3 and 4 days) coupled to morphology and gene expression analysis revealed rapid regeneration of skin without scarring in a marine teleost after a superficial wound caused by the loss of a large area of scales. The integrity of the integument, as assessed by quantification of extracellular matrix (ECM) gene transcripts (fn1a, colIα1, colVα2, colXα1, ogn1, ogn2, crtac1a, cyr61, pcna, krt2 and mmp9) was restored within 2 days...
February 4, 2018: Molecular Immunology
Yongxu Yang, Qi Qi, Yi Wang, Yaru Shi, Weili Yang, Yunzhu Cen, Endong Zhu, Xiaoxia Li, Di Chen, Baoli Wang
Emerging evidence suggests that cysteine-rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Madhuram Khandelwal, Vivek Anand, Sandeep Appunni, Amlesh Seth, Prabhjot Singh, Sandeep Mathur, Alpana Sharma
Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A...
January 24, 2018: Molecular and Cellular Biochemistry
Ho Bong Hyun, Jeong Yong Moon, Somi Kim Cho
Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5-fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), paclitaxel (PAC), and docetaxel (DOC). Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC50) and significantly reduced the viability of AGS-cyr61 cells compared with AGS cells...
January 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ki-Hyun Kim, Jong Hoon Won, Naiyuan Cheng, Lester F Lau
The expression of Ccn1 (Cyr61) is essential for cardiovascular development during embryogenesis, whereas in adulthood it is associated with inflammation, wound healing, injury repair, and related pathologies including fibrosis and cancer. Recent studies have found that CCN1 plays a critical role in promoting wound healing and tissue repair. Mechanistically, CCN1 functions through direct interaction with specific integrin receptors expressed in various cell types in the wound tissue microenvironment to coordinate diverse cellular functions for repair...
January 22, 2018: Journal of Cell Communication and Signaling
Gexin Zhao, Bau-Lin Huang, Diana Rigueur, Weiguang Wang, Chimay Bhoot, Kemberly R Charles, Jongseung Baek, Subburaman Mohan, Jie Jiang, Karen M Lyons
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermate...
January 19, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Jingang Deng, Xiaoxian Qian, Jianping Li, Yanghua Li, Yang Li, Yijun Luo
AIM: The aim is to evaluate serum cysteine-rich protein 61 (Cyr61) levels in patients with coronary artery disease (CAD). PATIENTS & METHODS: Serum Cyr61 levels were measured in 180 patients with CAD and 74 participants without CAD. RESULTS: Serum Cyr61 levels were significantly higher in CAD patients. Patients with acute coronary syndrome showed significantly higher Cyr61 than those with stable angina pectoris. Serum Cyr61 levels in complex lesion group were significantly higher...
January 18, 2018: Biomarkers in Medicine
Shui Yu, Yi-Jun Zeng, Xiao-Chuan Sun
The present study aimed to investigate whether the neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA‑22 expression was upregulated. In addition, downregulation of microRNA‑22 in HEB cells increased the mRNA expression levels of interleukin (IL)‑6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B‑cell lymphoma 2‑associated X protein (Bax) and caspase‑3 activity...
January 16, 2018: International Journal of Molecular Medicine
Tae Woo Jung, Changmuk Kang, Jiwon Goh, Soo In Chae, Hyoung-Chun Kim, Tae Jin Lee, A M Abd El-Aty, Ji Hoon Jeong
Wnt1-inducible signaling pathway protein-1 (WISP1) is a Cyr61/CTGF/NOV (CCN) family matricellular protein involved in adipogenesis and low-grade inflammation in obesity. However, the roles of WISP1 in hepatic steatosis and insulin resistance in skeletal muscle remain elusive. Mouse primary hepatocytes and differentiated mouse skeletal muscle cells (C2C12) were treated with various concentrations of WISP1 and the functions and signaling pathways were analyzed by Western blot analysis. In vivo transfection for WISP1 knockdown was also performed to examine the effects of WISP1 on hepatic steatosis and skeletal muscle insulin resistance...
January 10, 2018: Journal of Cellular Physiology
Nicoletta Zoppi, Nicola Chiarelli, Silvia Binetti, Marco Ritelli, Marina Colombi
Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with unknown molecular basis mainly characterized by generalized joint hypermobility, joint instability complications and minor skin changes. The phenotypic spectrum is broad and includes multiple associated symptoms shared with chronic inflammatory systemic diseases. The stricter criteria defined in the 2017 EDS nosology leave without an identity many individuals with symptomatic joint hypermobility and/or features of hEDS; for these patients, the term Hypermobility Spectrum Disorders (HSD) was introduced...
January 5, 2018: Biochimica et Biophysica Acta
Yawei Xu, Haijiao Chu, Yan Zhou, Junling Wang, Changying Dong, Rui Yin
Increasing evidence indicates that microRNAs(miRNAs) are often aberrantly expressed in osteosarcoma (OS) and play critical roles in OS tumorigenesis. Therefore, the discovery of miRNAs may provide a new and powerful tool for understanding the mechanismof OS initiation and development. The aim of this study was to investigate the functional significance of miR-365 and identify its possible mechanism in OS cells. Here, wefound that the expression level of miR-365 is significantly downregulated in OS tissues and cell lines, and its expression isassociated with the clinical stage, distant metastasis, tumor grade, and poor overall survival rate...
December 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhi-Qiang Li, Wei-Ru Wu, Chen Zhao, Chen Zhao, Xiao-Li Zhang, Zhong Yang, Jing Pan, Wei-Ke Si
Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)‑producing cells in liver fibrosis. Activated HSCs stimulate the proliferation and migration of hepatocellular carcinoma (HCC) cells. Cysteine‑rich 61 (CCN1/Cyr61) is an ECM protein. Our previous studies demonstrated that the expression of CCN1 was significantly higher in benign hepatic cirrhosis tissue and cancer‑adjacent hepatic cirrhosis tissues. CCN1 is a target gene of β‑catenin in HCC and promotes the proliferation of HCC cells...
March 2018: International Journal of Molecular Medicine
Hsiang-Lin Lee, Hui-Ling Chiou, Shian-Shiang Wang, Sheng-Chun Hung, Ming-Chih Chou, Shun-Fa Yang, Ming-Ju Hsieh, Ying-Erh Chou
OBJECTIVES: Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics...
December 22, 2017: Urologic Oncology
Bo Yang, Jiangdong Ni, Hui Long, Jun Huang, Cheng Yang, Xianzhe Huang
Osteoarthritis (OA) is the most prevalent degenerative joint disease with multifactorial etiology caused by risk factors. The degradation of aggrecan by upregulated ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is the key event in the development of OA. ADAMTS-4 contributes to aggrecan degradation in human OA. Cysteine-rich angiogenic inducer 61 (Cyr61), which is associated with diseases related to chronic inflammation, is found in articular cartilage from patients with osteoarthritis and appears to suppress ADAMTS-4 activity, possibly leading to chondrocyte cloning...
December 13, 2017: Journal of Cellular Biochemistry
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