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https://www.readbyqxmd.com/read/28819420/loss-of-complement-factor-h-in-plasma-increases-endothelial-cell-migration
#1
Ju Liu, Josephine Hoh
Tumor growth depends on angiogenesis, the growth of new blood vessels. Complement factor H (CFH) is a plasma glycoprotein that functions as a regulator of the complement system. The aim of this study is to delineate the role of CFH in angiogenesis. A conditional null allele of the Cfh gene was generated in C57BL/6J mice by flanking the exon 3 with loxP sites. The Cfh(flox/flox) mice were crossed with Rosa26-Cre mice to obtain the mice homozygotes of Cfh deletion (Cfh(-/-)). The Cfh(-/-) mice were examined by in vivo angiogenesis assays...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819185/deletion-of-ep4-in-s100a4-lineage-cells-reduces-scar-tissue-formation-during-early-but-not-later-stages-of-tendon-healing
#2
Jessica E Ackerman, Katherine T Best, Regis J O'Keefe, Alayna E Loiselle
Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818870/fra-2-negatively-regulates-postnatal-alveolar-septation-by-modulating-myofibroblast-function
#3
Kazuyuki Tsujino, John T Li, Tatsuya Tsukui, Xin Ren, Latifa Bakiri, Erwin F Wagner, Dean Sheppard
Mice that globally over-express the transcription factor, Fos-related antigen-2 (Fra-2), develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that over-express Fra-2 specifically in these cells types (α-SMA-rtTA; tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis, but developed a spontaneous emphysema-like phenotype characterized by alveolar enlargement...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#4
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28814342/septal-contributions-to-olfactory-bulb-interneuron-diversity-in-the-embryonic-mouse-telencephalon-role-of-the-homeobox-gene-gsx2
#5
Shenyue Qin, Stephanie M Ware, Ronald R Waclaw, Kenneth Campbell
BACKGROUND: Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified...
August 16, 2017: Neural Development
https://www.readbyqxmd.com/read/28811183/deletion-of-protein-kinase-d1-in-osteoprogenitor-cells-results-in-decreased-osteogenesis-in-vitro-and-reduced-bone-mineral-density-in-vivo
#6
Wendy B Bollag, Vivek Choudhary, Qing Zhong, Ke-Hong Ding, Jianrui Xu, Ranya Elsayed, Kanglun Yu, Yun Su, Lakiea J Bailey, Xing-Ming Shi, Mohammed Elsalanty, Maribeth H Johnson, Meghan E McGee-Lawrence, Carlos M Isales
Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates...
August 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28801621/efficient-generation-of-conditional-knockout-mice-via-sequential-introduction-of-lox-sites
#7
Takuro Horii, Sumiyo Morita, Mika Kimura, Naomi Terawaki, Mihiro Shibutani, Izuho Hatada
Conditional knockout using Cre/lox is essential for functional analysis of genes. CRISPR/Cas in combination with two sets of guide RNAs and a single-stranded oligonucleotide enables simultaneous insertion of two lox sequences. However, this method induces double-strand breaks at two sites on the same chromosome, which causes an undesirable chromosomal deletion and reduces the flanked lox (flox) rate. To solve this problem, we investigated a method that sequentially introduces each lox sequence at the 1-cell and 2-cell embryonic stages, respectively...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800750/angiopoietin-1-deficiency-increases-tumor-metastasis-in-mice
#8
Iacovos P Michael, Martina Orebrand, Marta Lima, Beatriz Pereira, Olga Volpert, Susan E Quaggin, Marie Jeansson
BACKGROUND: Angipoietin-1 activation of the tyrosine kinase receptor Tek expressed mainly on endothelial cells leads to survival and stabilization of endothelial cells. Studies have shown that Angiopoietin-1 counteracts permeability induced by a number of stimuli. Here, we test the hypothesis that loss of Angiopoietin-1/Tek signaling in the vasculature would increase metastasis. METHODS: Angiopoietin-1 was deleted in mice just before birth using floxed Angiopoietin-1 and Tek mice crossed to doxycycline-inducible bitransgenic ROSA-rtTA/tetO-Cre mice...
August 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28790014/bmp2-expression-in-the-endocardial-lineage-is-required-for-av-endocardial-cushion-maturation-and-remodeling
#9
Jacob G Saxon, Daniel R Baer, Julie A Barton, Travis Hawkins, Bingruo Wu, Thomas C Trusk, Stephen E Harris, Bin Zhou, Yuji Mishina, Yukiko Sugi
Distal outgrowth, maturation and remodeling of the endocardial cushion mesenchyme in the atrioventricular (AV) canal are the essential morphogenetic events during four-chambered heart formation. Mesenchymalized AV endocardial cushions give rise to the AV valves and the membranous ventricular septum (VS). Failure of these processes results in several human congenital heart defects. Despite this clinical relevance, the mechanisms governing how mesenchymalized AV endocardial cushions mature and remodel into the membranous VS and AV valves have only begun to be elucidated...
August 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28780076/bmi1-and-mel18-promote-colitis-associated-cancer-in-mice-via-reg3b-and-stat3
#10
Xicheng Liu, Wendi Wei, Xiaowei Li, Pengcheng Shen, Dapeng Ju, Zhen Wang, Rukui Zhang, Fu Yang, Chunyan Chen, Kun Cao, Guoli Zhu, Hongyan Chen, Liang Chen, Jianhua Sui, Erquan Zhang, Kaichun Wu, Fengchao Wang, Liping Zhao, Rongwen Xi
BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1) and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1(ΔIEC), Mel18(ΔIEC), DKO, and TKO mice)...
August 2, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28768721/the-glucocorticoid-receptor-in-monocyte-derived-macrophages-is-critical-for-cardiac-infarct-repair-and-remodeling
#11
Paolo Galuppo, Sabine Vettorazzi, Julian Hövelmann, Claus-Jürgen Scholz, Jan Peter Tuckermann, Johann Bauersachs, Daniela Fraccarollo
Cell- and tissue-specific actions of glucocorticoids are mediated by the glucocorticoid receptor. Here, we demonstrate that the glucocorticoid receptor (GR) in macrophages is essential for cardiac healing after myocardial infarction. Compared with GR(flox) (wild-type controls), GR(LysMCre) mice that lacked GR in myeloid cells showed increased acute mortality as a result of cardiac rupture. Seven days after left coronary artery ligation, GR(LysMCre) mice exhibited worse cardiac function and adverse remodeling associated with impaired scar formation and angiogenic response to ischemic injury...
August 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28752701/-effects-of-myeloid-specific-deficiency-of-fbxw7-on-lung-metastasis-of-murine-melanoma
#12
Zhang Wei, Lai Lihua, Wang Qingqing
Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm(-)FBXW7(f/f) and Lysm(+)FBXW7 (f/f) mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed...
March 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28749080/cellular-and-genetic-models-of-h6pdh-and-11%C3%AE-hsd1-function-in-skeletal-muscle
#13
Agnieszka E Zielinska, Rachel S Fletcher, Mark Sherlock, Craig L Doig, Gareth G Lavery
Glucocorticoids are important for skeletal muscle energy metabolism, regulating glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine dinucleotide phosphate-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum (SR) is integral to mediating the detrimental effects of glucocorticoid excess in muscle. 11β-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6-phosphate transporter (G6PT)-mediated G6P transport into the SR for its metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation...
July 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28747341/arginase1-deficiency-in-monocytes-macrophages-upregulates-inducible-nitric-oxide-synthase-to-promote-cutaneous-contact-hypersensitivity
#14
Jutamas Suwanpradid, Michael Shih, Lauren Pontius, Bin Yang, Anastasiya Birukova, Emma Guttman-Yassky, David L Corcoran, Loretta G Que, Robert M Tighe, Amanda S MacLeod
The innate immune components that modulate allergic contact hypersensitivity (CHS) responses are poorly defined. Using human skin from contact dermatitis patients and a mouse model of CHS, we find that hapten allergens disrupt the Arginase1 (Arg1) and inducible NO synthase (iNOS) dynamic in monocytes/macrophages (mono/MΦ), which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in MΦ develop increased CHS characterized by elevated ear thickening, mono/MΦ-dominated dermal inflammation, and increased iNOS and IL-6 expression compared with control mice...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28744254/metabolic-characterization-of-a-novel-ror%C3%AE-knockout-mouse-model-without-ataxia
#15
Cyrielle Billon, Sadichha Sitaula, Thomas P Burris
The retinoic acid receptor-related receptor α (RORα) is a nuclear receptor that plays an important role in regulation of metabolism and the immune system. Genetic deletion of the receptor yields mice with significant cerebellar developmental issues associated with severe ataxia. Although many metabolic studies have been performed in these models, the impaired locomotor activity of these mice is known to affect their normal mobility and feeding behaviors. This creates some difficulty in interpretation of the role of RORα in models of metabolic disease where feeding and muscle function is a critical component of the pathophysiology...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28727705/activation-of-the-rage-stat3-pathway-in-the-dorsal-root-ganglion-contributes-to-the-persistent-pain-hypersensitivity-induced-by-lumbar-disc-herniation
#16
Xin-Sheng Zhang, Xiao Li, Hai-Jie Luo, Zhu-Xi Huang, Cui-Cui Liu, Qing Wan, Shu-Wei Xu, Shao-Ling Wu, Song-Jian Ke, Chao Ma
BACKGROUND: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. OBJECTIVE: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. STUDY DESIGN: Controlled animal study...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28726785/jun-is-important-for-ocular-hypertension-induced-retinal-ganglion-cell-degeneration
#17
Stephanie B Syc-Mazurek, Kimberly A Fernandes, Richard T Libby
Ocular hypertension, a major risk factor for glaucoma, is thought to trigger glaucomatous neurodegeneration through injury to retinal ganglion cell (RGC) axons. The molecular signaling pathway leading from ocular hypertension to RGC degeneration, however, is not well defined. JNK signaling, a component of the mitogen-activated protein kinase (MAPK) family, and its canonical target, the transcription factor JUN, have been shown to regulate neurodegeneration in many different systems. JUN is expressed after glaucoma-relevant injuries and Jun deficiency protects RGCs after mechanical injury to the optic nerve...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28710293/probing-gata-factor-function-in-mouse-leydig-cells-via-testicular-injection-of-adenoviral-vectors
#18
Gervette M Penny, Rebecca B Cochran, Marjut Pihlajoki, Antti Kyrönlahti, Anja Schrade, Merja Häkkinen, Jorma Toppari, Markku Heikinheimo, David B Wilson
Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new Leydig cell ablation model based on Cre/Lox recombination of mouse Gata4 and Gata6, two genes implicated in the transcriptional regulation of steroidogenesis. The testicular interstitium of adult Gata4(flox/flox);Gata6(flox/flox) mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or GFP alone (Ad-GFP). The vectors efficiently and selectively transduced Leydig cells, as evidenced by GFP reporter expression...
July 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28699895/a-role-for-brg1-in-the-regulation-of-genes-required-for-development-of-the-lymphatic-system
#19
Ajeet Pratap Singh, Julie Foley, Arpit Tandon, Dhiral Phadke, H Karimi Kinyamu, Trevor K Archer
Lymphatic vasculature is an important part of the cardiovascular system with multiple functions, including regulation of the return of interstitial fluid (lymph) to the bloodstream, immune responses, and fat absorption. Consequently, lymphatic vasculature defects are involved in many pathological processes, including tumor metastasis and lymphedema. BRG1 is an important player in the developmental window when the lymphatic system is initiated. In the current study, we used tamoxifen inducible Rosa26CreERT2-BRG1floxed/floxed mice that allowed temporal analysis of the impact of BRG1 inactivation in the embryo...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28668388/ampk%C3%AE-1-deficiency-suppresses-brown-adipogenesis-in-favor-of-fibrogenesis-during-brown-adipose-tissue-development
#20
Junxing Zhao, Qiyuan Yang, Lupei Zhang, Xingwei Liang, Xiaofei Sun, Bo Wang, Yanting Chen, Meijun Zhu, Min Du
Brown adipose tissue (BAT) dissipates energy for thermogenesis which reduces or prevents obesity and metabolic dysfunction. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism and its activity is inhibited in the developing BAT due to obesity. We previously found that AMPK is required for brown fat development and thermogenic function, but the non-brown adipogenic differentiation of progenitor cells due to AMPKα1 deficiency has not been defined. We found that, in vivo, the thermogenic capacity and morphology of BAT were compromised due to AMPK deficiency, which was correlated with decreased progenitor density in BAT...
June 28, 2017: Biochemical and Biophysical Research Communications
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