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https://www.readbyqxmd.com/read/28620300/novel-anti-fibrotic-therapies
#1
REVIEW
Benita L McVicker, Robert G Bennett
Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Novel treatments have recently been identified that hold promise as potential therapeutic agents for cardiovascular diseases associated with fibrosis, as well as other fibrotic conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28573199/combinatorial-discovery-of-defined-substrates-that-promote-a-stem-cell-state-in-malignant-melanoma
#2
Douglas Zhang, Junmin Lee, Michael B Sun, Yi Pei, James Chu, Martha U Gillette, Timothy M Fan, Kristopher A Kilian
The tumor microenvironment is implicated in orchestrating cancer cell transformation and metastasis. However, specific cell-ligand interactions between cancer cells and the extracellular matrix are difficult to decipher due to a dynamic and multivariate presentation of many signaling molecules. Here we report a versatile peptide microarray platform that is capable of screening for cancer cell phenotypic changes in response to ligand-receptor interactions. Using a screen of 78 peptide combinations derived from proteins present in the melanoma microenvironment, we identify a proteoglycan binding and bone morphogenic protein 7 (BMP7) derived sequence that selectively promotes the expression of several putative melanoma initiating cell markers...
May 24, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28534975/resveratrol-inactivates-pi3k-akt-signaling-through-upregulating-bmp7-in-human-colon-cancer-cells
#3
Yu-Hua Zeng, Lin-Yun Zhou, Qian-Zhao Chen, Yang Li, Ying Shao, Wen-Yan Ren, Yun-Peng Liao, Han Wang, Jia-Hui Zhu, Ming Huang, Fang He, Jin Wang, Ke Wu, Bai-Cheng He
Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect...
May 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28527661/modulation-of-adipocyte-function-by-the-tgf-%C3%AE-family
#4
Yuhang Qiao, Shozo Tomonaga, Masashi Suenaga, Tohru Matsui, Masayuki Funaba
Members of the transforming growth factor-β (TGF-β) family are known to regulate the commitment of mesenchymal stem cells to an adipocyte lineage and the differentiation of preadipocytes to adipocytes. However, the roles of TGF-β family members in mature adipocytes are not known. The present study explored the modulation of cell function in 3T3-L1 adipocytes treated with the TGF-β family members TGF-β1, activin A, activin B, bone morphogenetic protein (BMP) 4, and BMP7. These TGF-β family members modulated the expression of some adipokines; activin A upregulated leptin expression, and activin B downregulated the expression of plasminogen activator inhibitor-1...
May 17, 2017: Cytokine
https://www.readbyqxmd.com/read/28526933/protection-of-tubular-epithelial-cells-during-renal-injury-via-post-transcriptional-control-of-bmp7
#5
Jiping Sun, Aiping Yin, Fei Zhao, Wenjing Zhang, Jia Lv, Jing Lv
Severe injury of renal tubular epithelial cells may cause acute renal failure, the progression of which results in renal fibrosis, and obstructive nephropathy. Transforming growth factor β 1 and bone morphogenic protein 7 (BMP7) play contradicting roles in and coordinate the process of epithelial-to-mesenchymal transition of renal tubular epithelial cells, but the molecular regulation of BMP7 remains ill-defined. Here, we addressed this question. We found that after induction of unilateral ureteral obstruction (UUO) in mice, the increases in BMP7 mRNA were much more pronounced than BMP7 protein in kidney, suggesting the presence of post-transcriptional control of BMP7...
May 19, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28508891/joint-morphogenetic-cells-in-the-adult-mammalian-synovium
#6
Anke J Roelofs, Janja Zupan, Anna H K Riemen, Karolina Kania, Sharon Ansboro, Nathan White, Susan M Clark, Cosimo De Bari
The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFP(high) perivascular population, and contribute to cartilage repair...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28501726/osteogenic-differentiation-of-mesenchymal-stem-cells-is-impaired-by-bone-morphogenetic-protein-7
#7
Paweena Wongwitwichot, Jasadee Kaewsrichan
PURPOSE: Mesenchymal stem cells (MSCs) are multipotent adult stem cells and present in practically all tissues but originally identified within the bone marrow (BM). The differentiation potential of these cells is generally impaired when culturing in vitro for cell expansion. The aim of this study is to speedily increase the numbers of bone marrow derived mesenchymal stem cells (BM-MSCs) with substantially maintaining their differentiation potential in vitro and improving bone formation in vivo...
May 11, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28496199/upregulation-and-biological-function-of-transmembrane-protein-119-in-osteosarcoma
#8
Zhen-Huan Jiang, Jun Peng, Hui-Lin Yang, Xing-Li Fu, Jin-Zhi Wang, Lei Liu, Jian-Nong Jiang, Yong-Fei Tan, Zhi-Jun Ge
Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28483168/hedgehog-gli1-signaling-regelates-differentiation-of-chicken-gallus-gallus-embryonic-stem-cells-to-male-germ-cells
#9
Dong Li, Shaoze Cheng, Wenhui Zhang, Man Wang, Changhua Sun, Chen Zhang, Yilin Wang, Jing Jin, Yani Zhang, Bichun Li
Gli1 is an important signaling molecular in Hedgehog signaling pathway. In our study, we explored the adjustment effect of Hedgehog-Gli1 signaling pathway on chicken male germ cells differentiation based on the transcriptome-wide analyses of chicken ESCs, primordial germ cells (PGCs) and spermatogonia stem cells (SSCs) that were associated with male germ cell differentiation. We screened out Hedgehog signaling pathway and identified 8 candidated differentially expressed genes (DEGs), Wnt3a, Wnt16, Wnt8a, HHIPL1, Gli1, BMP6, BMP7 and TTLL4...
February 10, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28470822/pericyte-derived-bone-morphogenetic-protein-4-underlies-white-matter-damage-after-chronic-hypoperfusion
#10
Maiko T Uemura, Masafumi Ihara, Takakuni Maki, Takayuki Nakagomi, Seiji Kaji, Kengo Uemura, Tomohiro Matsuyama, Raj N Kalaria, Ayae Kinoshita, Ryosuke Takahashi
Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. The aim of this study was to characterize signaling abnormalities of BMPs in sporadic SVD...
May 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28438174/exercise-attenuates-neurological-deficits-by-stimulating-a-critical-hsp70-nf-%C3%AE%C2%BAb-il-6-synapsin-i-axis-in-traumatic-brain-injury-rats
#11
Chung-Ching Chio, Hung-Jung Lin, Yu-Feng Tian, Yu-Chieh Chen, Mao-Tsun Lin, Cheng-Hsien Lin, Ching-Ping Chang, Chien-Chin Hsu
BACKGROUND: Despite previous evidence for a potent inflammatory response after a traumatic brain injury (TBI), it is unknown whether exercise preconditioning (EP) improves outcomes after a TBI by modulating inflammatory responses. METHODS: We performed quantitative real-time PCR (qPCR) to quantify the genes encoding 84 cytokines and chemokines in the peripheral blood and used ELISA to determine both the cerebral and blood levels of interleukin-6 (IL-6). We also performed the chromatin immunoprecipitation (ChIP) assay to evaluate the extent of nuclear factor kappa-B (NF-κB) binding to the DNA elements in the IL-6 promoter regions...
April 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#12
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications such as insulin resistance and non-alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28407692/microrna-137-inhibits-bmp7-to-enhance-the-epithelial-mesenchymal-transition-of-breast-cancer-cells
#13
Xuexiang Ying, Yunpo Sun, Pingqing He
Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth factor β 1 (TGFβ1)-mediated fibrosis through suppressing epithelial-mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the effects of TGFβ1 in breast cancer (BC) tumorigenesis-related EMT. Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we detected significantly lower levels of BMP7 and significantly higher levels of microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor breast tissue...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386343/signaling-by-tgf-betas-in-tubule-cultures-of-adult-rat-testis
#14
Kai-Hui Chan, Sebastian P Galuska, Pradeep Kumar Kudipudi, Mohammad Assad Riaz, Kate L Loveland, Lutz Konrad
Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28381236/microglia-activation-is-essential-for-bmp7-mediated-retinal-reactive-gliosis
#15
Subramanian Dharmarajan, Debra L Fisk, Christine M Sorenson, Nader Sheibani, Teri L Belecky-Adams
BACKGROUND: Our previous studies have shown that BMP7 is able to trigger activation of retinal macroglia. However, these studies showed the responsiveness of Müller glial cells and retinal astrocytes in vitro was attenuated in comparison to those in vivo, indicating other retinal cell types may be mediating the response of the macroglial cells to BMP7. In this study, we test the hypothesis that BMP7-mediated gliosis is the result of inflammatory signaling from retinal microglia. METHODS: Adult mice were injected intravitreally with BMP7 and eyes harvested 1, 3, or 7 days postinjection...
April 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28324064/bmp7-induces-uterine-receptivity-and-blastocyst-attachment
#16
Diana Monsivais, Caterina Clementi, Jia Peng, Paul T Fullerton, Renata Prunskaite-Hyyryläinen, Seppo J Vainio, Martin M Matzuk
In women, the window of implantation is limited to a brief 2- to 3-day period characterized by optimal levels of circulating ovarian hormones and a receptive endometrium. Although the window of implantation is assumed to occur 8 to 10 days after ovulation in women, molecular markers of endometrial receptivity are necessary to determine optimal timing prior to embryo transfer. Previous studies showed that members of the bone morphogenetic protein (BMP) family are expressed in the uterus necessary for female fertility; however, the role of BMP7 during implantation and in late gestation is not known...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28294194/phosphodiesterase-5-inhibition-preserves-renal-hemodynamics-and-function-in-mice-with-diabetic-kidney-disease-by-modulating-mir-22-and-bmp7
#17
Riccardo Pofi, Daniela Fiore, Rita De Gaetano, Giuseppe Panio, Daniele Gianfrilli, Carlotta Pozza, Federica Barbagallo, Yang Kevin Xiang, Konstantinos Giannakakis, Susanna Morano, Andrea Lenzi, Fabio Naro, Andrea M Isidori, Mary Anna Venneri
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260165/l-arginine-promotes-protein-synthesis-and-cell-growth-in-brown-adipocyte-precursor-cells-via-the-mtor-signal-pathway
#18
Xi Ma, Meng Han, Defa Li, Shengdi Hu, Kyler R Gilbreath, Fuller W Bazer, Guoyao Wu
L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h...
March 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/28219951/generation-of-thalamic-neurons-from-mouse-embryonic-stem-cells
#19
Atsushi Shiraishi, Keiko Muguruma, Yoshiki Sasai
Thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here we have succeeded in the generation of thalamic neurons from mouse ES cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28215684/expression-of-genes-involved-in-bmp-and-estrogen-signaling-and-ampk-production-can-be-important-factors-affecting-total-number-of-antral-follicles-in-ewes
#20
Golshan Foroughinia, Ali Fazileh, Shahin Eghbalsaied
Follicular growth and ovulation of healthy oocytes is a complicated process which is regulated by several endocrine and paracrine factors as well as cross-talk between the oocyte and its surrounding somatic cells. This study compared the expression profile of some candidate genes involved in BMP signaling as well as estrogen and AMPK production in cumulus-oocyte complex (COC) of small and large antral follicles and their associated somatic cell layers in ovaries from ewes with high- and low-antral follicle count (AFC)...
March 15, 2017: Theriogenology
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