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https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#1
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28339089/hmgb1-induces-lung-fibroblast-to-myofibroblast-differentiation-through-nf%C3%A2-%C3%AE%C2%BAb%C3%A2-mediated-tgf%C3%A2-%C3%AE-1-release
#2
Qiong Wang, Jun Wang, Junfang Wang, Shanchao Hong, Feifei Han, Jingyu Chen, Guoqian Chen
The proinflammatory factor high‑mobility group box protein 1 (HMGB1) has been implicated in the pathogenesis of lung fibrosis; however, the role of HMGB1 in lung fibrosis remains unclear. It has previously been reported that nuclear factor (NF)‑κB and transforming growth factor (TGF)‑β1 may be involved in lung fibrosis. Therefore, the present study aimed to examine the potential molecular mechanisms that underlie HMGB1‑induced lung fibrosis via the regulation of NF‑κB and TGF‑β1. The results demonstrated that HMGB1 stimulation increased the activation of NF‑κB and the release of TGF‑β1, as well as the expression of α‑smooth muscle actin (α‑SMA) and collagen I in human lung fibroblasts in vitro...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339087/regulation-of-intestinal-myofibroblasts-by-kras-mutated-colorectal-cancer-cells-through-heparin-binding-epidermal-growth-factor-like-growth-factor
#3
Hideyoshi Kawasaki, Takuya Saotome, Tatsuya Usui, Takashi Ohama, Koichi Sato
In colorectal cancer, gain-of-function mutations in KRas play a critical role in malignant transformation. Tumor growth in colorectal cancer is known to be promoted by the intestinal myofibroblasts (IMFs) that localize adjacent to the cancer cells, but the mechanisms of interaction between KRas-mutated cancer cells and the myofibroblasts remain unclear. Here, we investigated the effects of KRas-mutated cells on the behavior of myofibroblasts by using mouse primary IMFs and cells of an IMF cell line (LmcMF) and a mouse colon epithelial cell line (aMoC1)...
March 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28337443/urethral-reconstruction-using-mesothelial-cell-seeded-autogenous-granulation-tissue-tube-an-experimental-study-in-male-rabbits
#4
Shiwei Jiang, Zhonghua Xu, Yuanyuan Zhao, Lei Yan, Zunlin Zhou, Gangli Gu
Objective. This study was to evaluate the utility of the compound graft for tubularized urethroplasty by seeding mesothelial cells onto autogenous granulation tissue. Methods. Silastic tubes were implanted subcutaneously in 18 male rabbits, of which nine underwent omentum biopsies simultaneously for in vitro expansion of mesothelial cells. The granulation tissue covering the tubes was harvested 2 weeks after operation. Mesothelial cells were seeded onto and cocultured with the tissue for 7 days. A pendulous urethral segment of 1...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337224/gut-mesenchymal-stromal-cells-in-immunity
#5
REVIEW
Valeria Messina, Carla Buccione, Giulia Marotta, Giovanna Ziccheddu, Michele Signore, Gianfranco Mattia, Rossella Puglisi, Benedetto Sacchetti, Livia Biancone, Mauro Valtieri
Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28336812/tgf-%C3%AE-1-stimulates-hdac4-nucleus-to-cytoplasm-translocation-and-nadph-oxidase4-derived-reactive-oxygen-species-in-normal-human-lung-fibroblasts
#6
Weichao Guo, Shigeki Saito, Cecilia G Sanchez, Yan Zhuang, Rafael E Gongora Rosero, Bin Shan, Fayong Luo, Joseph A Lasky
Myofibroblasts are important mediators of fibrogenesis, thus blocking fibroblast to myofibroblast differentiation (FMD) may be an effective strategy to treat pulmonary fibrosis (PF). Previously we reported that HDAC4 activity is necessary for TGF-β1-induced human lung FMD. Here we show that TGF-β1 increases NOX4 mRNA and protein expression in normal human lung fibroblasts (NHLFs) and causes nuclear export of HDAC4. Application of the NOX family inhibitor, diphenyleneiodonium chloride (DPI), reduces TGF-β1-induced HDAC4 nuclear export, expression of the myofibroblast marker α-smooth muscle actin (α-SMA), and α-SMA fiber formation...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336721/tubule-derived-wnts-are-required-for-fibroblast-activation-and-kidney-fibrosis
#7
Dong Zhou, Haiyan Fu, Lu Zhang, Ke Zhang, Yali Min, Liangxiang Xiao, Lin Lin, Sheldon I Bastacky, Youhua Liu
Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction...
March 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28331757/inflammatory-myofibroblastic-tumor-of-the-breast-coexisting-with-pseudoangiomatous-stromal-hyperplasia
#8
Canan Kelten Talu, Yasemin Çakır, Ezgi Hacıhasanoğlu, Cem Leblebici, Şefika Aksoy, Mehmet Ali Nazlı
Inflammatory myofibroblastic tumors (IMTs) are uncommon breast lesions that consist of spindle cells accompanied by plasma cell-rich inflammatory infiltration, which may mimic breast cancer clinico-radiologically. A woman aged 38 years with a breast mass was referred to our general surgery clinic. The physical examination revealed a mass with irregular borders in the upper outer quadrant of the left breast. In mammography, the lesion was 15 mm in diameter with a spheric form and high density. Ultrasonographically, the mass was solid, heterogeneous, and hypoechoic with posterior enhancement...
October 2016: J Breast Health (2013)
https://www.readbyqxmd.com/read/28330809/piperine-attenuates-pathological-cardiac-fibrosis-via-ppar-%C3%AE-akt-pathways
#9
Zhen-Guo Ma, Yu-Pei Yuan, Xin Zhang, Si-Chi Xu, Sha-Sha Wang, Qi-Zhu Tang
Mitogen-activated protein kinases (MAPKs) and AMP-activated protein kinase α (AMPKα) play critical roles in the process of cardiac hypertrophy. Previous studies have demonstrated that piperine activates AMPKα and reduces the phosphorylation of extracellular signal-regulated kinase (ERK). However, the effect of piperine on cardiac hypertrophy remains completely unknown. Here, we show that piperine-treated mice had similar hypertrophic responses as mice treated with vehicle but exhibited significantly attenuated cardiac fibrosis after pressure overload or isoprenaline (ISO) injection...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28323397/in-vivo-response-to-decellularized-mesothelium-scaffolds
#10
Michael J Cronce, Renea A Faulknor, Irina Pomerantseva, Xiang-Hong Liu, Scott M Goldman, Emmanuel C Ekwueme, Olive Mwizerwa, Craig M Neville, Cathryn A Sundback
Biological surgical scaffolds are used in plastic and reconstructive surgery to support structural reinforcement and regeneration of soft tissue defects. Macrophage and fibroblast cell populations heavily regulate scaffold integration into host tissue following implantation. In the present study, the biological host response to a commercially available surgical scaffold (Meso BioMatrix Surgical Mesh (MBM)) was investigated for up to 9 weeks after subcutaneous implantation; this scaffold promoted superior cell migration and infiltration previously in in vitro studies relative to other commercially available scaffolds...
March 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28322247/tricyclic-antidepressants-promote-ceramide-accumulation-to-regulate-collagen-production-in-human-hepatic-stellate-cells
#11
Jennifer Y Chen, Benjamin Newcomb, Chan Zhou, Joshua V Pondick, Sarani Ghoshal, Samuel R York, Daniel L Motola, Nicolas Coant, Jae Kyo Yi, Cungui Mao, Kenneth K Tanabe, Irina Bronova, Evgeny V Berdyshev, Bryan C Fuchs, Yusuf Hannun, Raymond T Chung, Alan C Mullen
Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320829/tissue-engineering-functional-gastrointestinal-regions-the-importance-of-stem-and-progenitor-cells
#12
Andrew Trecartin, Tracy Grikscheit
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28320405/urinary-collagen-degradation-products-as-early-markers-of-progressive-renal-fibrosis
#13
Ryanne S Hijmans, Daniel Guldager Kring Rasmussen, Saleh Yazdani, Gerjan Navis, Harry van Goor, Morten Asser Karsdal, Federica Genovese, Jacob van den Born
BACKGROUND: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. METHODS: Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12)...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28316170/-advances-in-effects-of-integrin-linked-kinase-on-cutaneous-wound-healing-and-the-relative-mechanism
#14
R X Zhou, Y Y Li, W H Lin, G Li, J E Sun, W B Zhou
Previous studies have demonstrated that integrin-linked kinases (ILKs) are abundantly expressed in extracellular matrix (ECM) riche dermis, hair follicles, and basal cells of epidermis. ILKs are not only essential for the maintenance of skin structure, but also play important roles in wound healing. ILKs can promote the formation of granulation tissue by stimulating the proliferation of fibroblasts and secretion of ECM, accelerate wound contraction by inducing the differentiation of fibroblasts to myofibroblasts, and boost reepithelization by promoting proliferation, migration, and differentiation of keratinocytes and follicle epidermal stem cells...
March 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28315427/histologic-features-of-stromogenic-carcinoma-of-the-prostate-carcinomas-with-reactive-stroma-grade-3
#15
Andrea Diaz De Vivar, Mohammad Sayeeduddin, David Rowley, Antonio Cubilla, Brian Miles, Dov Kadmon, Gustavo Ayala
Prostatic carcinoma, like many other carcinomas, generates a stromal reaction. This phenomenon is well established in the scientific literature. The normal parenchymal smooth muscle phenotype switches to a myofibroblastic phenotype in response to the presence of cancer cells, with an expansion of the extracellular matrix compartment. The amount of reactive stroma is a predictor of biochemical recurrence in both radical prostatectomies and biopsies. It is a predictor of prostate cancer specific death in prostatectomies...
March 14, 2017: Human Pathology
https://www.readbyqxmd.com/read/28315313/transforming-growth-factors-%C3%AE-and-%C3%AE-are-essential-for-modeling-cholangiocarcinoma-desmoplasia-and-progression-in-a-three-dimensional-organotypic-culture-model
#16
Miguel A Manzanares, Akihiro Usui, Deanna J Campbell, Catherine I Dumur, Gabrielle T Maldonado, Michel Fausther, Jonathan A Dranoff, Alphonse E Sirica
To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM...
March 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28314802/an-ex-vivo-model-to-induce-early-fibrosis-like-changes-in-human-precision-cut-lung-slices
#17
Hani N Alsafadi, Claudia A Staab-Weijnitz, Mareike Lehmann, Michael Lindner, Britta Peschel, Melanie Königshoff, Darcy Elizabeth Wagner
IPF is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments which halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS)...
March 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#18
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314576/trpc6-and-kidney-disease-sclerosing-more-than-just-glomeruli
#19
Johannes Schlondorff
Fibrosis is a common response to injury but can also perpetuate tissue dysfunction. Transient receptor potential C6 (TRPC6) is implicated in cardiac and skin healing via regulation of myofibroblast differentiation. Wu et al. now demonstrate a role for TRPC6 in renal fibrosis, via a mechanism that also relies on TRPC3 and is antagonized by soluble klotho. Modulation of TRPC3/6 activity may provide a means of dampening the fibrotic response involved in chronic kidney disease progression.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28306368/spontaneous-regression-of-inflammatory-myofibroblastic-tumor-of-the-orbit-a-case-report-and-review-of-literature
#20
Larissa Habib, Jung Hoon Son, Carisa Petris, Michael Kazim
Inflammatory myofibroblastic tumor is a rare entity characterized by the presence of myofibroblasts and inflammatory cells within a fibrous stroma. It typically occurs in the pediatric population. The most common site of occurrence is the lung though it has been reported throughout the body. Although rare, it has been reported in the orbit. The clinical course is ill defined in the literature; here we report a case of pediatric IMT with delayed spontaneous regression.
March 17, 2017: Orbit
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