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Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Andrea Protti, Osamu Yamaguchi, Shizuo Akira, Ajay M Shah, Kazuhiko Nishida, Kinya Otsu
We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated.TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days post-operation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
Siying Ren, Yongfeng Luo, Hui Chen, David Warburton, Hilaire C Lam, Larry Wang, Ping Chen, Elizabeth P Henske, Wei Shi
The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mTORC1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver...
October 18, 2016: American Journal of Pathology
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk Jmk De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho associated protein kinase (ROCK) pathway in corpus cavernosum of patients with severe erectile dysfunction (ED) compared to healthy human corpus cavernosum, and to test the functional effects of two Rho Kinase Inhibitors (RKI) on erectile tissue of patients with severe ED, not responding to phosphodiesterase type 5 inhibitors (PDE5-i). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from individuals undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for qPCR)...
October 20, 2016: BJU International
Francesca Bianchini, Silvia Peppicelli, Pierangelo Fabbrizzi, Alessio Biagioni, Benedetta Mazzanti, Gloria Menchi, Lido Calorini, Alberto Pupi, Andrea Trabocchi
Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident...
October 19, 2016: Molecular and Cellular Biochemistry
Huafeng Wang, Huan Zhang, Yuqing Zhang, Dan Wang, Xixi Cheng, Fengrui Yang, Qi Zhang, Zhenyi Xue, Yan Li, Lijuan Zhang, Luhong Yang, Guolin Miao, Daiqing Li, Zhiyu Guan, Yurong Da, Zhi Yao, Fei Gao, Liang Qiao, Li Kong, Rongxin Zhang
Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver...
October 14, 2016: Oncotarget
Junko Nio-Kobayashi, Kaya Miyazaki, Kazuhisa Hashiba, Kiyoshi Okuda, Toshihiko Iwanaga
BACKGROUND: The mechanisms regulating the function and regression of the corpus luteum (CL) have not yet been elucidated in detail. The regressed CL of cows was previously reported to be filled with unusual vessels like arteriovenous anastomosis (AVA); however how these vessels are being established during luteolysis remains unknown. METHODS: The bovine CL at different luteal stages and regressing bovine CL induced by prostaglandin F2α (PGF) were histologically analyzed using light and electron microscopic levels...
October 19, 2016: Journal of Ovarian Research
Mariana Certal, Adriana Vinhas, Aurora Barros-Barbosa, Fátima Ferreirinha, Maria Adelina Costa, Paulo Correia-de-Sá
Nucleotides released during heart injury affect myocardium electrophysiology and remodelling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca(2) +]i accumulation and growth of DDR-2/a-SMA-expressing myofibroblasts from adult rat ventricles via P2Y4 and P2Y2 receptors activation, respectively. Ventricular myofibroblasts also express ADP-sensitive P2Yi, P2Yi2 and P2Yi3 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells...
October 18, 2016: Journal of Cellular Physiology
Man Koon Suh, Kyo Ho Lee, Aram Harijan, Hyung-Gu Kim, Euicheol C Jeong
BACKGROUND: Alloplastic materials are a mainstay in Asian rhinoplasty. However, the outline of alloplastic implants can become conspicuous over time in rhinoplasty patients, which is a significant cause for revision. In revision rhinoplasty, alloplastic materials can remain a viable and affordable option in Asian patients. The acellular dermal matrices (ADM) are often used to interface between the silicone material and the skin envelope. This study assesses histologic changes following implantation of ADM-covered silicone material in rats...
October 14, 2016: Journal of Craniofacial Surgery
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Anji Anura, Debanjan Das, Mousumi Pal, Ranjan Rashmi Paul, Soumen Das, Jyotirmoy Chatterjee
Oral sub-mucous fibrosis (OSF), a potentially malignant disorder, exhibits extensive remodeling of extra-cellular matrix in the form of sub-epithelial fibrosis which is a possible sequel of assaults from different oral habit related irritants. It has been assumed that micro/nanobio-mechanical imbalance experienced in the oral mucosa due to fibrosis may be deterministic for malignant potential (7-13%) of this pathosis. Present study explores changes in mechanobiological attributes of sub-epithelial connective tissue of OSF and the normal counterpart...
September 20, 2016: Journal of the Mechanical Behavior of Biomedical Materials
Huei-Fen Jheng, Motohiko Hirotsuka, Tsuyoshi Goto, Masayuki Shibata, Yasuki Matsumura, Teruo Kawada
SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein- LFSMP-or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 weeks. Renal morphology and protein expression were evaluated by histochemical staining and western blots...
October 17, 2016: Molecular Nutrition & Food Research
Jia Guo, Lili Yang, Yingjin Qiao, Zhangsuo Liu
Epithelial-mesenchymal transition (EMT) is important for diabetic nephropathy (DN). Podocytes are specialized epithelial cells, which form a major component of the glomerular filtration barrier. Podocyte damage has been suggested to be the primary mechanism behind the albuminuria associated with DN. The present study aimed to determine the function of glycogen synthase kinase (GSK)‑3β in EMT and barrier dysfunction of mouse podocytes exposed to high glucose (HG) conditions. Matured and differentiated podocytes were treated with normal glucose (NG), HG or NG + mannitol...
September 26, 2016: Molecular Medicine Reports
Shakilu Jumanne, Aika Shoo, Livin Mumburi, Larry Akoko, Patricia Scanlan, Michael McDermott
No abstract text is available yet for this article.
September 29, 2016: European Journal of Gastroenterology & Hepatology
Sadhvi Nithiananthan, Aileen Crawford, Johnathan Cooper Knock, Daniel W Lambert, Simon A Whawell
Fibroblasts are the major cellular component of connective tissue and experience mechanical perturbations due to matrix remodelling and interstitial fluid movement. Transforming growth factor β1 (TGF-β1) can promote differentiation of fibroblasts in vitro to a contractile myofibroblastic phenotype characterised by the presence of α-smooth muscle actin (α-SMA) rich stress fibres. To study the role of mechanical stimulation in this process, we examined the response of primary human fibroblasts to physiological levels of fluid movement and its influence on fibroblast differentiation and responses to TGF-β1...
October 17, 2016: Journal of Cellular Biochemistry
Shan-Shan Rao, Xiang-Yan Zhang, Ming-Jun Shi, Ying Xiao, Ying-Ying Zhang, Yuan-Yuan Wang, Chang-Zhi Zhang, Song-Jun Shao, Xin-Mei Liu, Bing Guo
BACKGROUND: Recent evidence suggests that a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has anti-fibrotic effect. However, the exact mechanism of its anti-fibrotic potential remains is unclear. In this study, we investigated the molecular mechanism of SAHA in attenuating pulmonary fibrosis by regulating stability of Smad7 in paraquat (PQ)-induced lung fibrosis animal model and cultured pulmonary fibroblasts. METHODS: Rats with paraquat-induced lung fibrosis were fed with a SAHA solution (15 mg/kg) by gastric gavage...
September 2016: Journal of Thoracic Disease
Wenting Ma, Le Tao, Xuefei Wang, Qinyi Liu, Wei Zhang, Qiuying Li, Chunfeng He, Dongying Xue, Jie Zhang, Cheng Liu
AIMS: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. METHODS: Mice underwent UUO followed by vehicle or sorafenib treatment...
October 17, 2016: Cellular Physiology and Biochemistry
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
A S Mansfield, S J Murphy, F R Harris, S I Robinson, R S Marks, S H Johnson, J B Smadbeck, G C Halling, E S Yi, D Wigle, G Vasmatzis, J Jen
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy...
October 14, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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