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https://www.readbyqxmd.com/read/29353817/transforming-growth-factor-%C3%AE-signaling-in-systemic-sclerosis
#1
Nolan B Ayers, Chen-Ming Sun, Shi-You Chen
Systemic sclerosis (SSc) is a complex, multiorgan autoimmune disease of unknown etiology. Manifestation of the disease results from an interaction of three key pathologic features including irregularities of the antigen-specific immune system and the non-specific immune system, resulting in autoantibody production, vascular endothelial activation of small blood vessels, and tissue fibrosis as a result of fibroblast dysfunction. Given the heterogeneity of clinical presentation of the disease, a lack of universal models has impeded adequate testing of potential therapies for SSc...
January 18, 2018: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29353059/ask-family-kinases-are-required-for-optimal-nlrp3-inflammasome-priming
#2
David E Place, Parimal Samir, Rajendra Karki, Benoit Briard, Peter Vogel, Thirumala-Devi Kanneganti
Activation of the multimeric inflammasome complex leads to inflammatory responses to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family Pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is tightly regulated to restrict excessive inflammation. Because NLRP3 responds broadly to cellular insults and regulates cell death similar to the stress-activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized that ASK1/2 may regulate NLRP3 activity...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#3
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29348826/interaction-of-macrophages-with-apoptotic-cells-inhibits-transdifferentiation-and-invasion-of-lung-fibroblasts
#4
Yong-Bae Kim, Young-So Yoon, Youn-Hee Choi, Eun-Mi Park, Jihee Lee Kang
The invasion of activated fibroblasts is a key mechanism of tissue fibrosis pathology. The recognition and uptake of apoptotic cells can induce the anti-fibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-β1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-β1- or EGF-treated mouse lung fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti-fibrotic effects of conditioned media, including transfection of macrophages with COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348470/fibroblast-growth-factor-21-increases-insulin-sensitivity-through-specific-expansion-of-subcutaneous-fat
#5
Huating Li, Guangyu Wu, Qichen Fang, Mingliang Zhang, Xiaoyan Hui, Bin Sheng, Liang Wu, Yuqian Bao, Peng Li, Aimin Xu, Weiping Jia
Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are well-documented, uncertainty about its role in regulating excessive energy intake remains. Here, we show that FGF21 improves systemic insulin sensitivity by promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21 levels positively correlate with the SAT area in insulin-sensitive obese individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to a level equivalent to that in obesity restores SAT mass and reverses insulin resistance in FGF21KO, but not in adipose-specific βklotho knockout mice...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348198/interleukin-10-stiffens-the-heart
#6
Daniela Cihakova
Cardiac-resident macrophages are a diverse population of cells that have a critical role in the pathogenesis of heart failure. A new understanding of communication between macrophages and cardiac fibroblasts could lead to novel therapeutic strategies for heart failure with preserved ejection function.
January 18, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#7
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29343843/cathelicidin-oa1-a-novel-antioxidant-peptide-identified-from-an-amphibian-accelerates-skin-wound-healing
#8
Xiaoqing Cao, Ying Wang, Chunyun Wu, Xiaojie Li, Zhe Fu, Meifeng Yang, Wenxin Bian, Siyuan Wang, Yongli Song, Jing Tang, Xinwang Yang
Cathelicidins play pivotal roles in host defense. The discovery of novel cathelicidins is important research; however, despite the identification of many cathelicidins in vertebrates, few have been reported in amphibians. Here we identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an amphibian species, Odorrana andersonii. Produced by posttranslational processing of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence of 'IGRDPTWSHLAASCLKCIFDDLPKTHN' and a molecular mass of 3038...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343655/spatiotemporal-alterations-of-autophagy-marker-lc3-in-rat-skin-fibroblasts-during-wound-healing-process
#9
Emiko Asai, Masaya Yamamoto, Kazuki Ueda, Satoshi Waguri
To investigate the possible implications of autophagy, one of the degradation pathways induced by metabolic stress, in the dynamic reconstructive process of wound healing, the appearance and changes of punctate structures for microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, were examined in a rat skin wound healing model. Although the ratio of LC3-II/LC3-I in Western blotting was not evidently changed during the wound healing process, LC3-positive dots were clearly observed in fibroblasts and myofibroblasts, and occasionally in macrophages, by immunohistofluorescence microscopy...
January 16, 2018: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/29342870/biomarkers-of-progression-after-hiv-acute-early-infection-nothing-compares-to-cd4%C3%A2-%C2%BA-t-cell-count
#10
Gabriela Turk, Yanina Ghiglione, Macarena Hormanstorfer, Natalia Laufer, Romina Coloccini, Jimena Salido, César Trifone, María Julia Ruiz, Juliana Falivene, María Pía Holgado, María Paula Caruso, María Inés Figueroa, Horacio Salomón, Luis D Giavedoni, María de Los Ángeles Pando, María Magdalena Gherardi, Roberto Daniel Rabinovich, Pedro A Pury, Omar Sued
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29339450/cardiac-macrophages-promote-diastolic-dysfunction
#11
Maarten Hulsmans, Hendrik B Sager, Jason D Roh, María Valero-Muñoz, Nicholas E Houstis, Yoshiko Iwamoto, Yuan Sun, Richard M Wilson, Gregory Wojtkiewicz, Benoit Tricot, Michael T Osborne, Judy Hung, Claudio Vinegoni, Kamila Naxerova, David E Sosnovik, Michael R Zile, Amy D Bradshaw, Ronglih Liao, Ahmed Tawakol, Ralph Weissleder, Anthony Rosenzweig, Filip K Swirski, Flora Sam, Matthias Nahrendorf
Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29338742/m2-polarized-tumor-associated-macrophages-facilitated-migration-and-epithelial-mesenchymal-transition-of-hcc-cells-via-the-tlr4-stat3-signaling-pathway
#12
Rong-Rong Yao, Jing-Huan Li, Rui Zhang, Rong-Xin Chen, Yan-Hong Wang
BACKGROUND: M2-polarized macrophages are tumor-associated-macrophages (TAMs), which are important contents of tumor-infiltrating immune cells. Toll-like receptor 4 (TLR4) is a molecular biomarker of tumor aggressiveness and poor prognosis. Toll-like receptors (TLRs) have important roles in the immune system and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized macrophages...
January 16, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29337327/modulating-inflammation-in-a-cutaneous-chronic-wound-model-by-il-10-released-from-collagen-silica-nanocomposites-via-gene-delivery
#13
Xiaolin Wang, Thibaud Coradin, Christophe Hélary
Cutaneous chronic wounds remain a major clinical challenge which requires the development of novel wound dressings. Previously, we showed that collagen-silica nanocomposites consisting of polyethyleneimine (PEI)-DNA complexes associated with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained production and release of biomolecules. Herein, we further explored the possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti-inflammatory cytokine, which favors tissue repair...
January 16, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29335509/salient-type-1-interleukin-1-receptor-expression-in-peripheral-non-immune-cells
#14
Anping Song, Ling Zhu, Gowthami Gorantla, Olimpia Berdysz, Stephanie A Amici, Mireia Guerau-de-Arellano, Kathryn M Madalena, Jessica K Lerch, Xiaoyu Liu, Ning Quan
Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have focused on the expression and function of IL-1R1 in immune cells. Here we performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the highest sensitivity of in situ detection of IL-1R1 mRNA and protein. Besides validating previously reported IL-1R1 expression in the endocrine tissues including pituitary and pancreas, our results refuted previously reported exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal root ganglia (DRG)...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29332923/heart-failure-as-an-aging-related-phenotype
#15
Hiroyuki Morita, Issei Komuro
The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure...
January 15, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#16
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29330743/acute-downregulation-of-mir-155-leads-to-a-reduced-collagen-synthesis-through-attenuating-macrophages-inflammatory-factor-secretion-by-targeting-ship1
#17
Longlong Yang, Lingying Liu, Huinan Ying, Yonghui Yu, Donghai Zhang, Huping Deng, Haijun Zhang, Jiake Chai
Fibrosis, tightly associated with fibroblasts collagen synthesis, is related closely with inflammatory response. Our previously study found that acute downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR-155 in reducing fibrosis. We first found that down-regulation of miR-155 inhibited macrophages transforming growth factor-β1 (TGF-β1) and IL-1β secretion. Next, we found that co-cultured with macrophages increased the proliferation and collagen synthesis of fibroblasts, and downregulation of miR-155 in macrophages could effectively attenuate the accelerative effects...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29328028/-skin-pathology-in-diabetes-mellitus-clinical-and-pathophysiological-correlations-review
#18
K Kochet, I Lytus, I Svistunov, O Sulaieva
Skin pathology is registered in vast majority of patients with diabetes mellitus (DM). Despite the abundance of publications on dermatological problems in DM, there is still a number of gaps to be discussed in terms of pathophysiological mechanisms. The goal of this review was to assess the mechanisms of development of different skin pathologies under DM. One of the key pathogenic mechanisms of skin lesions in diabetes is hyperglycemia and the effects of the advanced glycation end products, inducing oxidative stress, endothelial dysfunction and inflammation; that in its turn can accelerate the mechanisms of skin aging, the development of diabetic dermopathy and scleredema diabeticorum...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29327326/il-11-facilitates-a-novel-connection-between-ra-joint-fibroblasts-and-endothelial-cells
#19
Hatem A Elshabrawy, Michael V Volin, Abdul B Essani, Zhenlong Chen, Iain B McInnes, Katrien Van Raemdonck, Karol Palasiewicz, Shiva Arami, Mark Gonzalez, Hossam M Ashour, Seung-Jae Kim, Guofei Zhou, David A Fox, Shiva Shahrara
IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues...
January 11, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29325453/age-related-lung-tissue-remodeling-due-to-the-local-distribution-of-mmp-2-timp-2-tgf-%C3%AE-and-hsp70
#20
Z Vitenberga, M Pilmane
Lung tissue remodeling requires complex interactions of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor (TGF) family and heat shock protein 70 (Hsp70). We evaluated the appearance and distribution of MMP-2, TIMP-2, TGF-β1 and Hsp70 in lung tissue using immunohistochemistry. Stained structures were graded semiquantitatively. Overall, more MMP-2, TIMP-2, TGF-β1 and Hsp70 were observed in bronchial cartilage, bronchial and alveola repithelium, and among alveolar macrophages...
January 12, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
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