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Min Zhang, Ping Zhang, Yunsong Liu, Longwei Lv, Xiao Zhang, Hao Liu, Yongsheng Zhou
The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling...
February 21, 2017: Scientific Reports
Yu-Hwai Tsai, David R Hill, Namit Kumar, Sha Huang, Alana M Chin, Briana R Dye, Melinda S Nagy, Michael P Verzi, Jason R Spence
BACKGROUND & AIMS: The Lgr family of transmembrane proteins (Lgr4, 5, 6) act as functional receptors for R-spondin proteins (Rspo 1, 2, 3, 4), and potentiate Wnt signaling in different contexts. Lgr5 is arguably the best characterized of the Lgr family members in a number of adult and embryonic contexts in mice. However, the function of LGR family members in early embryonic development is unclear, and has not been explored during human development or tissue differentiation in detail. METHODS: We interrogated the function and expression of LGR family members using human pluripotent stem cell-derived tissues including definitive endoderm, mid/hindgut, and intestinal organoids...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
Yoon Jin Choi, Nayoung Kim, Hye Seung Lee, Seon Mee Park, Ji Hyun Park, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Jin-Wook Kim, Dong Ho Lee
BACKGROUND: The human leucine-rich repeat-containing G-protein coupled receptor (LGR) 5 and CD44 are one of the candidates for the marker of gastric cancer stem cells. We compared the expressions of two genes among control, dysplasia and cancer groups. METHODS: We compared the mRNA expression of LGR5, CD44 and CD44v8-10 and immunohistochemistry (IHC) of LGR5 and CD44 in gastric antral mucosa of 45 controls, 36 patients with gastric dysplasia, and 39 patients with early gastric cancer...
December 2016: Journal of Cancer Prevention
Mariya I Petrova, Elke Lievens, Tine L A Verhoeven, Jean M Macklaim, Gregory Gloor, Dominique Schols, Jos Vanderleyden, Gregor Reid, Sarah Lebeer
The probiotic Lactobacillus rhamnosus GR-1 has been documented to survive implantation onto the vaginal epithelium and interfere with urogenital pathogens. However, the molecular mechanisms involved are largely unknown. Here, we report for the first time the construction of dedicated knock-out mutants in L. rhamnosus GR-1 to enable the study of gene functions. In a search for genes responsible for the adherence capacity of L. rhamnosus GR-1, a genomic region encoding a protein with homology to lectin-like proteins was identified...
November 21, 2016: Scientific Reports
Maggie Y Jiang, Tammy L Lee, Su-Shin Hao, Sepi Mahooti, Stephen M Baird, Daniel J Donoghue, Martin Haas
Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples...
October 18, 2016: Oncotarget
Magdalena Żak, Thijs van Oort, Ferry G Hendriksen, Marie-Isabelle Garcia, Gilbert Vassart, Wilko Grolman
In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the activity of Wnt/β-catenin signaling is modulated by an interaction between LGR receptors and their ligands from the R-spondin family. The deficiency in Lgr4 and Lgr5 genes leads to developmental malformations and lethality...
2016: Frontiers in Cellular Neuroscience
Mark Trinder, Tim W McDowell, Brendan A Daisley, Sohrab N Ali, Hon S Leong, Mark W Sumarah, Gregor Reid
: Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide...
October 15, 2016: Applied and Environmental Microbiology
David A Quigley, Eve Kandyba, Phillips Huang, Kyle D Halliwill, Jonas Sjölund, Facundo Pelorosso, Christine E Wong, Gillian L Hirst, Di Wu, Reyno Delrosario, Atul Kumar, Allan Balmain
Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis...
July 26, 2016: Cell Reports
Paraskevi Apostolou, Maroulio Pertesi, Vassiliki Aleporou-Marinou, Constantine Dimitrakakis, Christos Papadimitriou, Evangelia Razis, Christos Christodoulou, George Fountzilas, Drakoulis Yannoukakos, Irene Konstantopoulou, Florentia Fostira
A recurrent large genomic rearrangement (LGR) encompassing exons 23 and 24 of the BRCA1 gene has been identified in breast-ovarian cancer families of Greek origin. Its breakpoints have been determined as c.5406 + 664_*8273del11052 (RefSeq: NM_007294.3) and a diagnostic PCR has been set up for rapid screening. In a series of 2,092 high-risk families fully screened for BRCA1 and BRCA2 germline mutations, we have found the deletion in 35 families (1.68%), representing 7.83% of the mutations identified in both genes and 10...
June 30, 2016: Clinical Genetics
Gui-Xun Shi, Wei-Wei Mao, Xin-Feng Zheng, Lei-Sheng Jiang
R-spondins are a family of four secreted proteins and act as agonists of the canonical Wnt/β-catenin signaling pathway. They are broadly expressed in different phases of skeleton tissues. Recently, three closely related leucine-rich repeat containing G-protein-coupled receptors (Lgr4/5/6) have been identified as the new and exact receptors of R-spondins. On the cell surface, R-spondins binding with Lgr4/5/6 and Znrf3/Rnf43 lead to reduced turnover of Wnts-receptors and potentiate Wnt/β-catenin signaling pathway which is critical for the control of bone development and remodeling...
November 2016: Progress in Biophysics and Molecular Biology
Chao Zhu, Xin-Feng Zheng, Yue-Hua Yang, Bo Li, Yu-Ren Wang, Sheng-Dan Jiang, Lei-Sheng Jiang
R-spondin proteins are identified as secreted agonists of the canonical Wnt/β-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In our in vitro experiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4...
August 2016: Cellular Signalling
Na Li, Shu Liu, Hui-Shan Zhang, Zhi-Li Deng, Hua-Shan Zhao, Qian Zhao, Xiao-Hua Lei, Li-Na Ning, Yu-Jing Cao, Hai-Bin Wang, Shuang Liu, En-Kui Duan
R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which largely rely on Wnt/β-catenin signaling. However, in the skin epithelium and hair follicles, the information about R-spondins is deficient, although the expressions and functions of their receptors, LGR4/5/6, have already been studied in detail...
April 20, 2016: International Journal of Molecular Sciences
Fujun Li, Chaohui Gu, Fengyan Tian, Zhankui Jia, Zhenglei Meng, Yinghui Ding, Jinjian Yang
Prostate cancer is the most common solid-organ malignancy and the second leading cause of cancer-related death in males. The oncogenic effect of leucine-rich repeat-containing G protein-coupled receptor (LGR) 4 has been recognized in the formation of various types of cancers, yet its regulatory mechanism in prostate cancer is still not fully understood. Previous study has shown that LGR4 may be a new responsive gene of interleukin-6 (IL-6) in cancer progression. In the present study, we established the LNCaP-IL-6+ cell subline by long-term incubation with a low concentration of IL-6 and explored the regulatory role of miR-218, a tumor-suppressing miRNA, in IL-6-induced LGR4 expression and LNCaP-IL-6+ cell proliferation and invasion...
May 2016: Oncology Reports
J T Zhang, W L Zhou, C He, T Liu, C Y Li, L Wang
5-Fluorouracil (5-FU) is widely used in chemotherapy for treatment of colorectal cancer. Leucine-rich repeat-containing G protein-coupled receptor (LGR) is known to participate in the occurrence and development of breast cancer by regulating the rebirth of tumor vessels. This study aimed to explore the proliferation and apoptosis of HCT116 colorectal cancer cells treated with 5-FU and related molecular mechanisms. 5-FU (20 μg/mL) was used to treat cultured HCT116 cells. An MTT test, flow cytometry, and colony formation assays were used to examine the proliferation and apoptosis of HCT116 cells...
March 4, 2016: Genetics and Molecular Research: GMR
Peiren Shan, Liang Dong, Akiko Maehara, Tamim M Nazif, Ziad A Ali, LeRoy E Rabbani, Mark A Apfelbaum, Kate Dalton, Charles C Marboe, Donna M Mancini, Gary S Mintz, Giora Weisz
We sought to explore differences in distribution and morphology of coronary lesions comparing cardiac allograft vasculopathy and native coronary atherosclerosis (NCA) using intravascular imaging with optical coherence tomography (OCT). At the time of routine surveillance angiography, 17 heart transplant (HT) recipients with a history of high-grade cellular rejection (HGR) and 43 HT recipients with none/mild (low)-grade rejection underwent OCT imaging of the left anterior descending and were compared to 60 patients with NCA without HT...
April 15, 2016: American Journal of Cardiology
Iolanda Cioffi, Lidia Santarpia, Andrea Vaccaro, Roberto Iacone, Giuseppe Labruna, Maurizio Marra, Franco Contaldo, Mette Kristensen, Fabrizio Pasanisi
In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different isocaloric lunch meals, consisting of (i) refined-grain pasta (RG+T), (ii) whole-grain pasta (WG+T), (iii) lemon juice-supplemented refined-grain pasta (LRG+T), and (iv) refined-grain pasta with legumes (RG+L), were administered to 8 healthy participants in a crossover design...
March 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Sin Woo Lee, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Seong Il Seo
OBJECTIVE: To examine radiological growth patterns as an indicator of renal tumor aggressiveness, we studied about the growth kinetics of small renal mass (SRM, ≤4 cm) and possible associated factors for high Fuhrman nuclear grade (≥3). MATERIALS AND METHODS: From January 1999 to May 2013, 112 cases (111 patients) diagnosed as renal cell carcinoma after surgical treatment were reviewed retrospectively. Patients who had at least two preoperative contrast-enhanced computed tomography scans more than 6 months apart were included...
April 2016: Urology
L Huber, C F M de Lange, U Krogh, D Chamberlin, N L Trottier
Forty lactating multiparous Yorkshire sows were used to test the hypothesis that reducing dietary CP and supplementing with crystalline amino acids (CAA) increases dietary N utilization for milk production during early and peak lactation. Sows were assigned to 1 of 4 diets: 1) 16.0% CP (as-fed; analyzed contents; HCP); 2) 15.7% CP (MHCP); 3) 14.3% CP (MLCP); 4) 13.2% CP (LCP); diet HCP was formulated using soybean meal and corn as the only Lys sources. The reduced CP diets contained CAA to meet requirements of the limiting AA...
November 2015: Journal of Animal Science
Mahesh Jingarwar, Anuradha Pathak, Navroop Kaur Bajwa, Ritesh Kalaskar
This paper reports case of pediatric localized gingival recession (LGR) in mandibular anterior region which was treated by using new innovative surgical approach, i.e. combination of frenectomy and vestibular extension. These interceptive surgeries not only gained sufficient width of attached gingival but also lower the attachment of labial frenum. How to cite this article: Jingarwar M, Pathak A, Bajwa NK, Kalaskar R. Vestibular Extension along with Frenectomy in Management of Localized Gingival Recession in Pediatric Patient: A New Innovative Surgical Approach...
September 2015: International Journal of Clinical Pediatric Dentistry
Vanessa Chantreau, Bruck Taddese, Mathilde Munier, Louis Gourdin, Daniel Henrion, Patrice Rodien, Marie Chabbert
The thyrotropin receptor (TSHR) is a G protein-coupled receptor (GPCR) that is member of the leucine-rich repeat subfamily (LGR). In the absence of crystal structure, the success of rational design of ligands targeting the receptor internal cavity depends on the quality of the TSHR models built. In this subfamily, transmembrane helices (TM) 2 and 5 are characterized by the absence of proline compared to most receptors, raising the question of the structural conformation of these helices. To gain insight into the structural properties of these helices, we carried out bioinformatics and experimental studies...
2015: PloS One
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