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Claudia Landi, Elena Bargagli, Alfonso Carleo, Rosa Metella Refini, David Bennett, Laura Bianchi, Giuseppe Cillis, Antje Prasse, Luca Bini, Paola Rottoli
Objective: SSc is a rare severe connective tissue disorder. Its prognosis is mainly related to the development of pulmonary fibrosis (PF)-SSc and pulmonary arterial hypertension. No known therapy for PF-SSc modifies progressive lung fibrotic involvement. Research is therefore aimed at a deeper understanding of complex pathogenetic mechanisms and the possibility of new prognostic biomarkers and therapeutic targets. Methods: Towards the first of these aims, we conducted functional proteomic analysis of bronchoalveolar lavage samples from PF-SSc patients and smoker and non-smoker controls...
September 17, 2018: Rheumatology
Mengqian Li, Xian-Yang Qin, Yutaka Furutani, Ikuyo Inoue, Sanae Sekihara, Hiroyuki Kagechika, Soichi Kojima
Acute liver injury (ALI) is highly lethal acute liver failure caused by different etiologies. Transforming growth factor β (TGF-β) is a multifunctional cytokine and a well-recognized inducer of apoptotic and necrotic cell death in hepatocytes. Latent TGF-β is activated partly through proteolytic cleavage by a serine protease plasma kallikrein (PLK) between the R58 and L59 residues of its propeptide region. Recently, we developed a specific monoclonal antibody to detect the N-terminal side LAP degradation products ending at residue R58 (R58 LAP-DPs) that reflect PLK-dependent TGF-β activation...
September 12, 2018: Biochemical and Biophysical Research Communications
Elena De Vita, Peter Schüler, Scott Lovell, Jasmin Lohbeck, Sven Kullmann, Eitan Rabinovich, Amiram Sananes, Bernd Heßling, Veronique Hamon, Niv Papo, Jochen Heß, Edward W Tate, Nikolas Gunkel, Aubry K Miller
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6...
September 13, 2018: Journal of Medicinal Chemistry
Mario Navarrete, Julie Ho, Ravi C Dwivedi, Nora Choi, Peyman Ezzati, Victor Spicer, Rakesh C Arora, Claudio Rigatto, John A Wilkins
The processes involved in the initiation of acute kidney injury (AKI) following cardiopulmonary bypass (CPB) are thought to occur during the intraoperative period. Such a rapid development might indicate that some of the inductive events are not dependent on de novo protein synthesis, raising the possibility that changes in activities of pre-existing enzymes could contribute to the development of AKI. Activity-based protein profiling (ABPP) was used to compare the serine hydrolase enzyme activities present in the urines of CPB patients who subsequently developed AKI versus those who did not (non-AKI) during the intra- and immediate postoperative periods...
September 19, 2018: Journal of Proteome Research
M Li, F Jia, H Zhou, J Di, M Yang
OBJECTIVE: The aim of this study was to elaborate the influence of changing energy metabolism pattern of renal tubular epithelial cells in the process of renal interstitial fibrosis on podocytes. Meanwhile, we also investigated the relationship between energy metabolism pattern and the development of renal interstitial fibrosis. MATERIALS AND METHODS: We established a model of renal interstitial fibrosis by unilateral ureteral obstruction (UUO). The protein and messenger RNA (mRNA) expression of fibrosis signs, such as α-smooth muscle actin (α-SMA) and fibronectin (FN) were detected...
August 2018: European Review for Medical and Pharmacological Sciences
P Przybyłowski, G Wasilewski, E Koc-Żórawska, J Małyszko
Development of arterial hypertension is to some extent related to decreased activity of the kallikrein-kinin system. This poorly understood hormonal system consists of blood proteins playing a role in the process of inflammation, coagulation, blood pressure control, and pain conduction. The system consists of kallikreins (plasma and tissue), kallistatin, kininogens, kinins (bradykinin, kallidin-lizynobradykinin), kininases (I and II), and membrane receptors of bradykinin. The aim of the study was the assessment of kallistatin in correlation to blood pressure value in heart transplant recipients...
September 2018: Transplantation Proceedings
Yuhua Huang, Liangyu Zhao, Chencheng Yao, Chao Yang, Zijue Zhu, Peng Li, Ruhui Tian, Huixing Chen, Zuping He, Zheng Li
OBJECTIVES: To investigate the effect of kallikrein-related peptidase KLK1 on azoospermic mice induced by busulfan and mouse spermatogonial stem cell. METHODS: Mice were treated with a single intraperitoneal injection of busulfan, and 4 weeks later, they received a daily intraperitoneal injection of KLK1 at different doses for another 4 weeks. Eight weeks after the busulfan treatment, all mice were sacrificed and their testes were collected for histological evaluation, immunostaining and protein extraction...
August 29, 2018: Urology
Ran Zhang, Liang Peng, Haihong Ran, Yongyan Fan, Yu Zhao, Feng Cao
The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is expressed in the vasculature; our previous work showed that FXR regulated vascular reactivity through NO mechanism. The underlying mechanism for the regulation of vascular tension by FXR remains unclear. The present work was designed to investigate whether FXR regulates calcium homeostasis in aortic vascular smooth muscle cells (VSMCs). Protein abundances of angiotensin II type 1 and 2 receptors (AT₁R, AT₂R), bradykinin type 1 and 2 receptors (B₁R, B₂R), and the inositol 1,4,5-trisphosphate receptor (IP₃R) were analyzed by western blotting...
August 24, 2018: Chinese Journal of Physiology
Nikolas Khoury, Eleni Zingkou, Georgios Pampalakis, Michail Sofopoulos, Vassilis Zoumpourlis, Georgia Sotiropoulou
Kallikrein-related peptidase 6 (KLK6) is a serine protease that is aberrantly altered in various types of cancer but its role in non-melanoma skin cancer has not been investigated. KLK6 is active in epidermis and has been linked to normal skin differentiation. Thus, we investigated whether it could be implicated in skin tumorigenesis in vivo. Carcinogenesis was induced in Klk6-/- mice by epidermal application of DMBA/TPA and multistage skin tumor development and progression was monitored closely until squamous cell carcinomas (SCCs) and invasive tumors formed...
August 23, 2018: Carcinogenesis
Anezka C Rubin de Celis Ferrari, João Glasberg, Rachel P Riechelmann
Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment...
August 20, 2018: Clinics
Meng Wu, Yeping Yang, Meng Wang, Fangfang Zeng, Qin Li, Wenjuan Liu, Shizhe Guo, Min He, Yi Wang, Jie Huang, Linuo Zhou, Yiming Li, Ji Hu, Wei Gong, Zhaoyun Zhang
Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms. Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats...
2018: Frontiers in Pharmacology
S De Maat, Z L M Hofman, C Maas
We thank Drs Loffredo and Marone for their interest in our article and correspondence, which summarizes their impressive scientific contributions to the complex field of vascular biology. In our review, we provide an overview on the role of the plasma contact system, classically seen as part of the coagulation system, in hereditary angioedema [1]. The active role of the contact system in this pathology is evident, as both C1 esterase inhibitor C1INH deficiency and gain-of-function mutations in factor XII (FXII) result in hereditary angioedema...
August 21, 2018: Journal of Thrombosis and Haemostasis: JTH
Matthew D Morrison, Linda Jackson-Boeters, Zia A Khan, Michael S Shimizu, Jason H Franklin, Kevin Fung, John H J Yoo, Mark R Darling
Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid and proteins in PA specimens to determine a KLK expression profile for this tumor. Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to quantitative real-time reverse transcription polymerase chain reaction to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13, and KLK8 proteins were then evaluated via immunostaining techniques...
August 17, 2018: Head and Neck Pathology
Miroslava Didiasova, Lukasz Wujak, Liliana Schaefer, Malgorzata Wygrecka
Factor XII (FXII) is a protease that is mainly produced in the liver and circulates in plasma as a single chain zymogen. Following contact with negatively charged surfaces, FXII is converted into the two-chain active form, FXIIa. FXIIa initiates the intrinsic blood coagulation pathway via activation of factor XI. Furthermore, it converts plasma prekallikrein to kallikrein (PK), which reciprocally activates FXII and liberates bradykinin from high molecular weight kininogen. In addition, FXIIa initiates fibrinolysis via PK-mediated urokinase activation and activates the classical complement pathway...
November 2018: Cellular Signalling
Daniela Loessner, Peter Goettig, Sarah Preis, Johanna Felber, Holger Bronger, Judith A Clements, Julia Dorn, Viktor Magdolen
Aberrant levels of kallikrein-related peptidases (KLK1-15) have been linked to cancer cell proliferation, invasion and metastasis. In ovarian cancer, the KLK proteolytic network has a crucial role in the tissue and tumor microenvironment. Publically available ovarian cancer genome and expression data from multiple patient cohorts show an upregulation of most KLKs. Areas covered: Here, we review the expression levels of all 15 members of this family in normal and ovarian cancer tissues, categorizing them into highly and moderately or weakly expressed KLKs, and their association with patient prognosis and survival...
September 2018: Expert Opinion on Therapeutic Targets
Kerstin Göbel, Susann Eichler, Heinz Wiendl, Triantafyllos Chavakis, Christoph Kleinschnitz, Sven G Meuth
Background: The interaction of coagulation factors has been shown to go beyond their traditional roles in hemostasis and to affect the development of inflammatory diseases. Key molecular players, such as fibrinogen, thrombin, or factor XII have been mechanistically and epidemiologically linked to inflammatory disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), and colitis. Objectives: To systematically review the evidence for a role of coagulation factors, especially factor XII, fibrinogen, and thrombin in inflammatory disorders like MS, RA, and bowel disorders...
2018: Frontiers in Immunology
Milos Brankovic, K Martijn Akkerhuis, Henk Mouthaan, Alina Constantinescu, Kadir Caliskan, Jan van Ramshorst, Tjeerd Germans, Victor Umans, Isabella Kardys
BACKGROUND: Our aim was to explore potential use of temporal profiles of seven emerging cardio-renal and two pulmonary candidate biomarkers for predicting future adverse clinical outcome in stable patients with chronic heart failure (CHF). METHODS: In 263 CHF patients, we determined the risk of a composite endpoint of HF-hospitalization, cardiac death, LVAD-placement and heart transplantation in relation to repeatedly assessed (567 samples in total) blood biomarker levels, and slopes of their temporal trajectories (i...
August 3, 2018: International Journal of Cardiology
Bruno Censori, T Partziguian, V Bonito, M Sgarzi, R Riva, D Alimonti, E Agazzi, M Vedovello, B Frigeni, E Venturelli, S La Gioia, V Barcella, L Daleffe, L Longhi, F Ferri, R Cosentini, M R Rottoli
INTRODUCTION: Orolingual angioedema (OA) is a known adverse effect of intravenous (i.v.) alteplase. We analyzed all patients treated with i.v. alteplase for stroke at our hospital since approval of i.v. thrombolysis in Italy in 2004 to assess the incidence of this complication. PATIENTS AND RESULTS: Four hundred thirty-three patients received alteplase for stroke from April 2004 to May 2017. Two women developed OA (0.4%; 95% confidence interval 0.1 to 1.6%). Angioedema was mild in one case and severe in the other, with massive swelling of the lips, tongue, and oropharyngeal mucosa, and oropharyngeal bleeding, requiring intubation...
August 6, 2018: Neurological Sciences
Ting Qiu, Maria J Chiuchiolo, Adele S Whaley, Anthony R Russo, Dolan Sondhi, Stephen M Kaminsky, Ronald G Crystal, Odelya E Pagovich
BACKGROUND: Hereditary angioedema (HAE) is a life-threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1EI), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems...
July 30, 2018: Allergy
Christopher J D Wallis, Mohammad R Akbari, Steven A Narod, Robert K Nam
No abstract text is available yet for this article.
December 1, 2017: Journal of the National Cancer Institute
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