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Fibrogenesis

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https://www.readbyqxmd.com/read/29789683/bmp-2-restoration-aids-in-recovery-from-liver-fibrosis-by-attenuating-tgf-%C3%AE-1-signaling
#1
Yueh-Hua Chung, Ying-Hsien Huang, Tien-Huei Chu, Chun-Lin Chen, Pey-Ru Lin, Shih-Chung Huang, Deng-Chyang Wu, Chao-Cheng Huang, Tsung-Hui Hu, Ying-Hsien Kao, Ming-Hong Tai
Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29788096/pnaktide-ameliorates-renal-interstitial-fibrosis-through-inhibition-of-sodium-potassium-adenosine-triphosphatase-mediated-signaling-pathways-in-unilateral-ureteral-obstruction-mice
#2
Xi Cheng, Yi Song, Yu Wang
Background: Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO. Methods: UUO was performed on male C57BL/6J mice...
May 17, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29781524/tgf-%C3%AE-signalling-in-renal-fibrosis-from-smads-to-non-coding-rnas
#3
Patrick Ming-Kuen Tang, Ying-Ying Zhang, Thomas Shiu-Kwong Mak, Philip Chiu-Tsun Tang, Xiao-Ru Huang, Hui-Yao Lan
Transforming growth factor-β (TGF-β) is the key player in tissue fibrosis. However, antifibrotic therapy targeting this multifunctional protein may interfere other physiological processes to cause side effects. Thus, precise therapeutic targets are needed to be identified by further understanding the underlying mechanisms of TGF-β1 signalling during fibrogenesis. Equilibrium of Smad signalling is crucial for TGF-β-mediated renal fibrosis, where Smad3 is pathogenic but Smad2 and Smad7 are protective. The activation of TGF-β1/Smad signalling triggers extracellular matrix deposition, and local myofibroblast generation and activation...
May 21, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29760499/hepatic-stellate-cells-secrete-ccl5-to-induce-hepatocyte-steatosis
#4
Byeong-Moo Kim, Ahmed Maher Abdelfattah, Robin Vasan, Bryan C Fuchs, Michael Y Choi
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are known to contribute to fibrosis, but less is known about their function during NAFLD's early stages prior to fibrosis. We developed an ex vivo assay that cocultures primary HSCs from mouse models of liver disease with healthy hepatocytes to study their interaction...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29753790/il-17-promotes-scar-formation-by-inducing-macrophage-infiltration
#5
Julei Zhang, Qiao Qiao, Mengdong Liu, Ting He, Jihong Shi, Xiaozhi Bai, Yijie Zhang, Yan Li, Weixia Cai, Shichao Han, Hao Guan, Dahai Hu
Trauma or burn injuries that affect the deep dermis often produce a hypertrophic scar, which limits patients' joint movement and generates an aesthetic problem. Inflammation is believed to be one of the main pathogenic mechanisms. We found that IL-17 was increased in scar tissues from patients with hypertrophic scar compared with normal skin. Recombinant mouse IL-17 was subcutaneously injected into mice that underwent full-thickness excision surgery to investigate the role of IL-17 in scar formation. Mice stimulated with IL-17 showed aggravated fibrogenesis, delayed wound healing, and increased inflammation...
May 11, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29739813/interleukin-1-%C3%AE-activates-a-myc-dependent-metabolic-switch-in-kidney-stromal-cells-necessary-for-progressive-tubulointerstitial-fibrosis
#6
Dario R Lemos, Michael McMurdo, Gamze Karaca, Julia Wilflingseder, Irina A Leaf, Navin Gupta, Tomoya Miyoshi, Koichiro Susa, Bryce G Johnson, Kirolous Soliman, Guanghai Wang, Ryuji Morizane, Joseph V Bonventre, Jeremy S Duffield
Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids...
May 8, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29738802/intravoxel-incoherent-motion-mri-derived-parameters-and-t2-relaxation-time-for-noninvasive-assessment-of-renal-fibrosis-an-experimental-study-in-a-rabbit-model-of-unilateral-ureter-obstruction
#7
Sungmin Woo, Jeong Yeon Cho, Sang Youn Kim, Seung Hyup Kim
PURPOSE: To evaluate the association of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) MRI-derived parameters, and T2* relaxation time with histopathological changes observed during renal fibrogenesis in a rabbit model of unilateral ureter obstruction (UUO). METHODS: Twenty New Zealand White rabbits underwent baseline MRI followed by surgery (sham or UUO) and then follow-up MRI at postoperative day (POD) 0, 3, 7, and 14. Hematoxylin and eosin and Masson's trichrome staining was performed to evaluate cell density and area of fibrosis...
May 5, 2018: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/29733296/foxm1-is-a-critical-driver-of-lung-fibroblast-activation-and-fibrogenesis
#8
Loka R Penke, Jennifer M Speth, Vijaya L Dommeti, Eric S White, Ingrid L Bergin, Marc Peters-Golden
While the transcription factor forkhead box M1 (FOXM1) is well known as a proto-oncogene, its potential role in lung fibroblast activation has never been explored. Here, we show that FOXM1 is more highly expressed in fibrotic than in normal lung fibroblasts in humans and mice. FOXM1 was required not only for cell proliferation in response to mitogens, but also for myofibroblast differentiation and apoptosis resistance elicited by TGF-β. The lipid mediator PGE2, acting via cAMP signaling, was identified as an endogenous negative regulator of FOXM1...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29702491/acute-kidney-injury-to-chronic-kidney-disease-transition-insufficient-cellular-stress-response
#9
Sarah A Strausser, Daisuke Nakano, Tomokazu Souma
PURPOSE OF REVIEW: Recent epidemiological and preclinical mechanistic studies provide strong evidence that acute kidney injury (AKI) and chronic kidney disease (CKD) form an interconnected syndrome. Injured kidneys undergo a coordinated reparative process with an engagement of multiple cell types after injury; however, maladaptation to the injury subjects kidneys to a vicious cycle of fibrogenesis and nephron loss. In this review, we will outline and discuss the pathogenesis of AKI-to-CKD transition with an emphasis on dysregulated 'cellular stress adaptation' as a potential therapeutic target...
April 26, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29700280/altered-akap12-expression-in-portal-fibroblasts-and-liver-sinusoids-mediates-transition-from-hepatic-fibrogenesis-to-fibrosis-resolution
#10
Hye Shin Lee, Jinhyeok Choi, Taekwon Son, Hee-Jun Wee, Sung-Jin Bae, Ji Hae Seo, Ji Hyun Park, Soo Hyung Ryu, Danbi Lee, Myoung Kuk Jang, Eunsil Yu, Young-Hwa Chung, Kyu-Won Kim
Liver fibrosis can be reversed by removing its causative injuries; however, the molecular mechanisms mediating the resolution of liver fibrogenesis are poorly understood. We investigate the role of a scaffold protein, A-Kinase Anchoring Protein 12 (AKAP12), during liver fibrosis onset, and resolution. Biliary fibrogenesis and fibrosis resolution was induced in wild-type (WT) or AKAP12-deficient C57BL/6 mice through different feeding regimens with 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing chow...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29699061/expression-of-fibroblast-growth-factor-21-and-%C3%AE-klotho-regulates-hepatic-fibrosis-through-the-nuclear-factor-%C3%AE%C2%BAb-and-c-jun-n-terminal-kinase-pathways
#11
Kyong Joo Lee, Yoon Ok Jang, Seung-Kuy Cha, Moon Young Kim, Kyu-Sang Park, Young Woo Eom, Soon Koo Baik
Background/Aims: Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver. Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells...
April 27, 2018: Gut and Liver
https://www.readbyqxmd.com/read/29696816/deletion-of-smad4-attenuates-the-hepatic-inflammation-and-fibrogenesis-during-nonalcoholic-steatohepatitis-progression
#12
Geng Qin, Guo Zhen Wang, Dan Dan Guo, Ru-Xue Bai, Miao Wang, Shi Yu Du
OBJECTIVE: To explore the effects of Smad4 deletion on inflammation and fibrogenesis during nonalcoholic steatohepatitis (NASH) progression. METHODS: We collected 56 liver tissues from NASH patients (NASH group) and 60 normal liver tissues from patients received liver resection for trauma (control group). Smad4Co/Co mice and wild-type (WT) mice were used to construct NASH model by high-fat diet (HFD) or methionine- and choline-deficient (MCD) diet. Hematoxylin and eosin (HE) staining and Tunnel assay were performed to observe pathological changes and apoptosis of liver tissues, respectively, quantitative real-time polymerase chain reaction (qRT-PCR) to detect expressions of inflammatory, fibrogenesis and apoptosis-related genes, and immunohistochemistry to determine proteins expressions of Smad4, MCP-1 and α-SMA...
April 25, 2018: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/29696080/therapeutic-effects-of-serum-extracellular-vesicles-in-liver-fibrosis
#13
Li Chen, Ruju Chen, Sherri Kemper, Min Cong, Hong You, David R Brigstock
The lack of approved therapies for hepatic fibrosis seriously limits medical management of patients with chronic liver disease. Since extracellular vesicles (EVs) function as conduits for intercellular molecular transfer, we investigated if EVs from healthy individuals have anti-fibrotic properties. Hepatic fibrogenesis or fibrosis in carbon tetrachloride (CCl4 )- or thioacetic acid-induced liver injury models in male or female mice were suppressed by serum EVs from normal mice (EVN) but not from fibrotic mice (EVF)...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29689549/cardiomyocyte-derived-mir-328-promotes-cardiac-fibrosis-by-paracrinely-regulating-adjacent-fibroblasts
#14
Dandan Zhao, Cui Li, He Yan, Tianyu Li, Ming Qian, Nan Zheng, Hua Jiang, Li Liu, Bozhi Xu, Qiuxia Wu, Xuelian Li, Haihai Liang, Hongli Shan
BACKGROUND/AIMS: In our previous study, we demonstrated that elevated expression of miR-328 is a potent determinant of cardiac fibrosis during myocardial infarction (MI). In the present study, histological examination revealed progressive fibrosis in transgenic mice overexpressing cardiomyocyte-specific miR-328. This study investigated whether the transfer of miR-328 from cardiomyocytes (CMs) to cardiac fibroblasts (CFs) in a paracrine manner contributes to myocardial fibrosis. METHODS: Myocardial infarction was established by the occlusion of the left coronary artery...
April 19, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29686697/ppar-%C3%AE-antagonizes-hypoxia-induced-activation-of-hepatic-stellate-cell-through-cross-mediating-pi3k-akt-and-cgmp-pkg-signaling
#15
Qinghui Zhang, Shihao Xiang, Qingqian Liu, Tao Gu, Yongliang Yao, Xiaojie Lu
Background and Aims: Accumulating evidence reveals that PPAR γ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPAR γ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods: Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPAR γ agonist rosiglitazone...
2018: PPAR Research
https://www.readbyqxmd.com/read/29683732/lncrna-pfal-promotes-lung-fibrosis-through-ctgf-by-competitively-binding-mir-18a
#16
Xuelian Li, Tong Yu, Huitong Shan, Hua Jiang, Jian Sun, Xiaoguang Zhao, Wei Su, Lida Yang, Hongli Shan, Haihai Liang
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic parenchymal lung disease of unknown etiology and lacks an effective intervention. Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but the role of lncRNAs in lung fibrosis is not fully understood. In the present study, we identified that lncRNA NONMMUT021928, designated as pulmonary fibrosis-associated lncRNA (PFAL), was up-regulated in the lungs of mice with experimental lung fibrosis, and in TGF-β1-induced fibrotic lung fibroblasts...
April 23, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29679639/decoding-fibrosis-mechanisms-and-translational-aspects
#17
Liliana Schaefer
Fibrosis, a complex process of abnormal tissue healing which inevitably leads to loss of physiological organ structure and function, is a world-wide leading cause of death. Despite a large body of research over the last two decades, antifibrotic approaches are mainly limited to organ replacement therapy generating high costs of medical care. In this translational issue, a unique group of basic and clinical researchers provide meaningful answers to a desperate call of society for effective antifibrotic treatments...
April 18, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29669342/nr4a1-is-involved-in-fibrogenesis-in-ovarian-endometriosis
#18
Xinliu Zeng, Zhang Yue, Ying Gao, Guosong Jiang, Fuqing Zeng, Ying Shao, Jiayu Huang, Minuo Yin, Yajie Li
BACKGROUND/AIMS: Excess fibrosis may lead to chronic pain, scarring, and infertility as endometriosis develops and progresses. The pathogenesis of endometriosis has been linked to transforming growth factor-β (TGF-β), the most potent promoter of fibrosis. METHODS: Levels of NR4A1 and P-NR4A1 protein in human endometrial and endometriotic tissue were assessed by western blotting and immunohistochemistry. The expression levels of fibrotic markers in stromal cells were evaluated by real-time PCR...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29665133/isolation-of-a-unique-hepatic-stellate-cell-population-expressing-integrin-%C3%AE-8-from-embryonic-mouse-livers
#19
Tomohiro Ogawa, Yuchang Li, Ingrid Lua, Andrea Hartner, Kinji Asahina
BACKGROUND: Hepatic stellate cells (HSCs) play an important role in liver fibrogenesis. However, little is known about their phenotype and role in liver development. The aim of this study is to identify specific markers for embryonic HSCs. RESULTS: Using antibodies against ALCAM and PDPN, we separated mesothelial cells (MCs) and HSCs from developing livers and identified integrin α8 (ITGA8) as a marker for embryonic desmin+ HSCs that are preferentially localized near the developing liver surface and α-smooth muscle actin+ perivascular mesenchymal cells around the vein...
April 17, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29660654/assessment-of-the-possible-roles-of-sb-269970-versus-ketanserin-on-carbon-tetrachloride-induced-liver-fibrosis-in-rats-oxidative-stress-tgf-%C3%AE-1-induced-hscs-activation-pathway
#20
Marwa Ahmed Amin Atallah, Samah M Elaidy, Mona K Tawfik
BACKGROUND: In liver fibrosis, a major morbid and mortal disease, oxidative stress motivation of hepatic stellate cells (HSCs)-into myofibroblasts terminated in collagen deposition remain the key pathophysiological deal. Serotonin (5-HT) through its HSCs-expressed receptors, especially 5-HT2A and 7, shows crucial events in fibrogenesis of chronic liver diseases. Molecular hepatic oxidative stress-fibrotic roles of 5-HT2A and 7 receptors antagonists (ketanserin and SB-269970 respectively) are still a challenging issue...
November 28, 2017: Pharmacological Reports: PR
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