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Collagen dysfunction

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https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#1
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29158499/cardiac-myocyte-mir-29-promotes-pathological-remodeling-of-the-heart-by-activating-wnt-signaling
#2
Yassine Sassi, Petros Avramopoulos, Deepak Ramanujam, Laurenz Grüter, Stanislas Werfel, Simon Giosele, Andreas-David Brunner, Dena Esfandyari, Aikaterini S Papadopoulou, Bart De Strooper, Norbert Hübner, Regalla Kumarswamy, Thomas Thum, Xiaoke Yin, Manuel Mayr, Bernhard Laggerbauer, Stefan Engelhardt
Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29145467/adenosine-lidocaine-and-mg2-alm-fluid-therapy-attenuates-systemic-inflammation-platelet-dysfunction-and-coagulopathy-after-non-compressible-truncal-hemorrhage
#3
Hayley Letson, Geoffrey Dobson
BACKGROUND: Systemic inflammation and coagulopathy are major drivers of injury progression following hemorrhagic trauma. Our aim was to examine the effect of small-volume 3% NaCl adenosine, lidocaine and Mg2+ (ALM) bolus and 0.9% NaCl/ALM 'drip' on inflammation and coagulation in a rat model of hemorrhagic shock. METHODS: Sprague-Dawley rats (429±4 g) were randomly assigned to: 1) shams, 2) no-treatment, 3) saline-controls, 4) ALM-therapy, and 5) Hextend®. Hemorrhage was induced in anesthetized-ventilated animals by liver resection (60% left lateral lobe and 50% medial lobe)...
2017: PloS One
https://www.readbyqxmd.com/read/29144435/dysregulated-collagen-homeostasis-by-matrix-stiffening-and-tgf-%C3%AE-1-in-fibroblasts-from-idiopathic-pulmonary-fibrosis-patients-role-of-fak-akt
#4
Alícia Giménez, Paula Duch, Marta Puig, Marta Gabasa, Antoni Xaubet, Jordi Alcaraz
Idiopathic pulmonary fibrosis (IPF) is an aggressive disease in which normal lung parenchyma is replaced by a stiff dysfunctional scar rich in activated fibroblasts and collagen-I. We examined how the mechanochemical pro-fibrotic microenvironment provided by matrix stiffening and TGF-β1 cooperates in the transcriptional control of collagen homeostasis in normal and fibrotic conditions. For this purpose we cultured fibroblasts from IPF patients or control donors on hydrogels with tunable elasticity, including 3D collagen-I gels and 2D polyacrylamide (PAA) gels...
November 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29141501/transient-hypertension-after-spinal-cord-injury-leads-to-cerebrovascular-endothelial-dysfunction-and-fibrosis
#5
Aaron A Phillips, Nusrat Matin, Mengyao Jia, Jordan W Squair, Aaron Monga, Mei Mu Zi Zheng, Rahul Sachdeva, Andrew Yung, Shea Hocolaski, Stacy L Elliott, Piotr Kozlowski, Anne Dorrance, Ismail Laher, Phil Ainslie, Andrei V Krassioukov
We aimed to create a clinically-relevant preclinical model of transient hypertension, and then evaluate the pathophysiological cerebrovascular processes resulting from this novel stimulus, which has recently been epidemiologically linked to cerebrovascular disease. We first developed a clinically-relevant model of transient hypertension, secondary to induced autonomic dysreflexia after spinal cord injury, and demonstrated that in both patients and rats this stimulus leads to drastic acute cerebral hyper-perfusion...
November 15, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29138968/mitochondrial-dysfunctions-contribute-to-energy-deficits-in-rodent-model-of-hepatic-encephalopathy
#6
Saurabh Dhanda, Aditya Sunkaria, Avishek Halder, Rajat Sandhir
Perturbations in the cerebral energy metabolism are anticipated to be an important factor by which ammonia may exert its toxic effects on the central nervous system. The present study was designed to investigate the role of impaired mitochondrial functions and cerebral energy metabolism in the development hepatic encephalopathy (HE) induced by of bile duct ligation (BDL). After four weeks of BDL, a significant increase in hepatic hydroxyproline and collagen content was observed which confirmed biliary fibrosis...
November 14, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29138834/mechanism-of-free-radical-generation-in-platelets-and-primary-hepatocytes-a-novel-electron-spin-resonance-study
#7
Chiun-Lang Wang, Po-Sheng Yang, Jeng-Ting Tsao, Thanasekaran Jayakumar, Meng-Jiy Wang, Joen-Rong Sheu, Duen-Suey Chou
Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D‑galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH•) in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138820/matrine-suppresses-cardiac-fibrosis-by-inhibiting-the-tgf%C3%A2-%C3%AE-smad-pathway-in-experimental-diabetic-cardiomyopathy
#8
Yong Zhang, Lei Cui, Gongchang Guan, Junkui Wang, Chuan Qiu, Tielin Yang, Yan Guo, Zhongwei Liu
Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138674/exercise-training-restores-cardiac-microrna-1-and-microrna-29c-to-nonpathological-levels-in-obese-rats
#9
André C Silveira, Tiago Fernandes, Úrsula P R Soci, João L P Gomes, Diego L Barretti, Glória G F Mota, Carlos Eduardo Negrão, Edilamar M Oliveira
We previously reported that aerobic exercise training (AET) consisted of 10 weeks of 60-min swimming sessions, and 5 days/week AET counteracts CH in obesity. Here, we evaluated the role of microRNAs and their target genes that are involved in heart collagen deposition and calcium signaling, as well as the cardiac remodeling induced by AET in obese Zucker rats. Among the four experimental Zucker groups: control lean rats (LZR), control obese rats (OZR), trained lean rats (LZR + TR), and trained obese rats (OZR + TR), heart weight was greater in the OZR than in the LZR group due to increased cardiac intramuscular fat and collagen...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#10
Dounia Abbadi, Fanny Laroumanie, Mathilde Bizou, Joffrey Pozzo, Danièle Daviaud, Christine Delage, Denis Calise, Fréderique Gaits-Iacovoni, Marianne Dutaur, Florence Tortosa, Edith Renaud-Gabardos, Victorine Douin-Echinard, Anne-Catherine Prats, Jerome Roncalli, Angelo Parini, Nathalie Pizzinat
Aims: Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results: We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells...
November 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29133362/three-month-endothelial-human-endothelin-1-overexpression-causes-blood-pressure-elevation-and-vascular-and-kidney-injury
#11
Suellen C Coelho, Olga Berillo, Antoine Caillon, Sofiane Ouerd, Júlio C Fraulob-Aquino, Tlili Barhoumi, Stefan Offermanns, Pierre Paradis, Ernesto L Schiffrin
Endothelium-derived endothelin (ET)-1 has been implicated in the development of hypertension and end-organ damage, but its exact role remains unclear. We have shown that tamoxifen-inducible endothelium-restricted human ET-1 overexpressing (ieET-1) mice exhibited blood pressure rise after a 3-week induction in an ET type A (ETA) receptor-dependent manner, in absence of vascular and renal injury. It is unknown whether long-term ET-1 overexpression results in sustained blood pressure elevation and vascular and renal injury...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#12
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121102/histopathologic-and-immunohistochemical-features-of-capsular-tissue-around-failed-ahmed-glaucoma-valves
#13
Alka Mahale, Fatma Fikri, Khitam Al Hati, Sami Al Shahwan, Ibrahim Al Jadaan, Hind Al Katan, Rajiv Khandekar, Azza Maktabi, Deepak P Edward
Impervious encapsulation around Ahmed glaucoma valve (AGV) results in surgical failure raising intraocular pressure (IOP). Dysregulation of extracellular matrix (ECM) molecules and cellular factors might contribute to increased hydraulic resistance to aqueous drainage. Therefore, we examined these molecules in failed AGV capsular tissue. Immunostaining for ECM molecules (collagen I, collagen III, decorin, lumican, chondroitin sulfate, aggrecan and keratan sulfate) and cellular factors (αSMA and TGFβ) was performed on excised capsules from failed AGVs and control tenon's tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29120671/erythropoietin-reduces-collagen-deposition-after-myocardial-infarction-but-does-not-improve-cardiac-function
#14
Fernanda G Pessoa, Charles Mady, Keila C B Fonseca, Adriana M Oliveira-Fonoff, Vera M C Salemi, Mauricio R Jordao, Fabio Fernandes, Felix J A Ramires
Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into Control (CT), Control+EPO (CT+EPO), Infarcted+EPO (MI+EPO), and Infarcted (MI). The interstitial collagen volume fraction (ICVF) was quantified. Echocardiography was performed. We quantified ADMA and glutathione by ELISA, and RT-PCR to assess apoptosis and inflammation...
November 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29119568/unchanged-mitochondrial-phenotype-but-accumulation-of-lipids-in-the-myometrium-in-obese-pregnant-women
#15
Christiane Marie Bourgin Folke Gam, Lea Hüche Larsen, Ole Hartvig Mortensen, Line Engelbrechtsen, Steen Seier Poulsen, Klaus Qvortrup, Elisabeth Reinhart Mathiesen, Peter Damm, Bjørn Quistorff
KEY POINTS: Obesity during pregnancy and childbirth is associated with labour dystocia leading to instrumental or operative delivery, but the underlying pathophysiological mechanisms remain unclear and insufficient uterine contractility has been suggested. This study examined whether reduced myometrial mitochondrial capacity or quantity could contribute as a pathophysiological mechanism to labour dystocia. Data did not support reduced myometrial mitochondrial capacity or quantity in the myometrium at term in obese women, but a reduced myocyte density with increased triglyceride content was demonstrated, which could lead to poorer uterine contractility...
November 9, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29115435/human-umbilical-cord-mesenchymal-stem-cells-alleviate-interstitial-fibrosis-and-cardiac-dysfunction-in-a-dilated-cardiomyopathy-rat-model-by-inhibiting-tnf%C3%A2-%C3%AE-and-tgf%C3%A2-%C3%AE-1-erk1-2-signaling-pathways
#16
Changyi Zhang, Guichi Zhou, Yezeng Chen, Sizheng Liu, Fen Chen, Lichun Xie, Wei Wang, Yonggang Zhang, Tianyou Wang, Xiulan Lai, Lian Ma
Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord‑derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin‑induced rat model of DCM. Male Lewis rats (aged 8‑weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1x106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle‑injected and negative control rats...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109726/il-36%C3%AE-regulates-tubulointerstitial-inflammation-in-the-mouse-kidney
#17
Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29101178/heart-functional-and-structural-compendium-of-cardiosplenic-and-cardiorenal-networks-in-acute-and-chronic-heart-failure-pathology
#18
Ganesh V Halade, Vasundhara Kain, Kevin A Ingle
Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, the HF research is focused on left ventricle (LV) pathology. Here, we determined the comprehensive functional analysis of LV using echocardiography in transition from acute HF (AHF) to progressive CHF pathology and develop a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically-induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall-thinning and 20-30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2-4 months old; n=50)...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29098359/a-murine-model-for-human-eco-syndrome-reveals-a-critical-role-of-intestinal-cell-kinase-in-skeletal-development
#19
Mengmeng Ding, Li Jin, Lin Xie, So Hyun Park, Yixin Tong, Di Wu, A Bobby Chhabra, Zheng Fu, Xudong Li
An autosomal-recessive inactivating mutation R272Q in the human intestinal cell kinase (ICK) gene caused profound multiplex developmental defects in human endocrine-cerebro-osteodysplasia (ECO) syndrome. ECO patients exhibited a wide variety of skeletal abnormalities, yet the underlying mechanisms by which ICK regulates skeletal development remained largely unknown. The goal of this study was to understand the structural and mechanistic basis underlying skeletal anomalies caused by ICK dysfunction. Ick R272Q knock-in transgenic mouse model not only recapitulated major ECO skeletal defects such as short limbs and polydactyly but also revealed a deformed spine with defective intervertebral disk...
November 2, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29097327/gallic-acid-attenuates-pulmonary-fibrosis-in-a-mouse-model-of-transverse-aortic-contraction-induced-heart-failure
#20
Li Jin, Zhe Hao Piao, Simei Sun, Bin Liu, Yuhee Ryu, Sin Young Choi, Gwi Ran Kim, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice...
October 30, 2017: Vascular Pharmacology
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