1. IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesisMarchien G. Dallinga, Yasmin I. Habani, Richelle P. Kayser, Cornelis J. F. van Noorden, Ingeborg Klaassen, Reinier O. Schlingemann, 2020, original scientific article Abstract: Purpose
We have previously identified insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) as essential proteins for tip cell maintenance and sprouting angiogenesis. In this study, we aim to identify other IGF family members involved in endothelial sprouting angiogenesis.
Methods
Effects on sprouting were analyzed in human umbilical vein endothelial cells (HUVECs) using the spheroid-based sprouting model, and were quantified as mean number of sprouts per spheroid and average sprout length. RNA silencing technology was used to knockdown gene expression. Recombinant forms of the ligands (IGF1 and IGF2, insulin) and the IGF-binding proteins (IGFBP) 3 and 4 were used to induce excess effects. Effects on the tip cell phenotype were analyzed by measuring the fraction of CD34+ tip cells using flow cytometry and immunohistochemistry in a 3D angiogenesis model. Experiments were performed in the presence and absence of serum.
Results
Knockdown of IGF2 inhibited sprouting in HUVECs, in particular when cultured in the absence of serum, suggesting that components in serum influence the signaling of IGF2 in angiogenesis in vitro. We then determined the effects of IGFBP3 and IGFBP4, which are both present in serum, on IGF2-IGF1R signaling in sprouting angiogenesis in the absence of serum: knockdown of IGFBP3 significantly reduced sprouting angiogenesis, whereas knockdown of IGFBP4 resulted in increased sprouting angiogenesis in both flow cytometry analysis and immunohistochemical analysis of the 3D angiogenesis model. Other IGF family members except INSR did not affect IGF2-IGF1R signaling.
Conclusions
Serum components and IGF binding proteins regulate IGF2 effects on sprouting angiogenesis. Whereas IGFBP3 acts as co-factor for IGF2-IGF1R binding, IGFBP4 inhibits IGF2 signaling. Keywords: Angiogenesis, tip cells, IGF2, IGF binding proteins, endothelial cells, cultured cells, endothelial growth factors Published in DiRROS: 23.07.2024; Views: 112; Downloads: 131
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2. Autologous platelet and extracellular vesicle-rich plasma as therapeutic fluid : a reviewKaja Troha, Domen Vozel, Matevž Arko, Apolonija Bedina Zavec, Drago Dolinar, Matej Hočevar, Zala Jan, Matic Kisovec, Boštjan Kocjančič, Ljubiša Pađen, Manca Pajnič, Samo Penič, Anna Romolo, Neža Repar, Vesna Spasovski, Nejc Steiner, Vid Šuštar, Aleš Iglič, Damjana Drobne, Ksenija Kogej, Saba Battelino, Veronika Kralj-Iglič, 2023, review article Keywords: platelet-rich plasma, platelets, centrifugation, extracellular vesicles, small cellular particles, wound healing, regeneration, fresh-frozen plasma, intercellular signaling peptides and proteins Published in DiRROS: 26.01.2024; Views: 517; Downloads: 246
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3. Analyte-driven clustering of bio-conjugated magnetic nanoparticlesTilen Potisk, Jurij Sablić, Daniel Svenšek, Elena Sanz-de Diego, Francisco J. Teran, Matej Praprotnik, 2023, original scientific article Keywords: biochemistry, nanoparticles, magnetic nanoparticles, proteins, biosensors Published in DiRROS: 16.03.2023; Views: 718; Downloads: 293
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4. Gene expression levels of the prolyl hydroxylase domain proteins PHD1 and PHD2 but not PHD3 are decreased in primary tumours and correlate with poor prognosis of patients with surgically resected non-small-cell lung cancerAna Koren, Matija Rijavec, Tomaž Krumpestar, Izidor Kern, Aleksander Sadikov, Tanja Čufer, Peter Korošec, 2021, original scientific article Abstract: Background: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). Methods: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. Results: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. Conclusions: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC. Keywords: non-small-cell lung carcinoma, prognosis, non-small cell lung cancer, mRNA expression, prolyl hydroxylase domain proteins Published in DiRROS: 21.05.2021; Views: 1405; Downloads: 989
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5. Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary diseaseDenise Traxler, Matthias Zimmermann, Elisabeth Simader, Elisa Einwallner, Dragan Copic, Alexandra Graf, Thomas Mueller, Cecilia Veraar, Mitja Lainščak, Robert Marčun, Mitja Košnik, Matjaž Fležar, Aleš Rozman, Peter Korošec, 2020, original scientific article Abstract: Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown. Methods: In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data. Results: HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival. Conclusions: Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality. Keywords: biomarkers, heat-shock proteins, chronic obstructive pulmonary disease, urine, heat shock protein 27 Published in DiRROS: 25.01.2021; Views: 1643; Downloads: 1133
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6. Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolutionBasil J. Greber, Daniel Boehringer, Vlatka Godinić Mikulčić, Ana Crnković, Michael Ibba, Ivana Weygand-Durašević, Nenad Ban, 2012, original scientific article Keywords: archaeal proteins, cryoelectron microscopy, Methanobacteriaceae, prokaryotic initiation, factors, protein biosynthesis, ribosome subunits, archaeal, ribosomes Published in DiRROS: 07.05.2020; Views: 1946; Downloads: 1255
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7. RNA-dependent cysteine biosynthesis in bacteria and archaeaTakahito Mukai, Ana Crnković, Takuya Umehara, Natalia N. Ivanova, Nikos C. Kyrpides, Dieter Söll, 2017, original scientific article Keywords: amino acyl-tRNA synthetases, archaea, archaeal proteins, bacteria, computational biology, crystallography, X-ray, genetic code, genome, archaeal, genome, bacterial, phosphoserine, protein binding, protein biosynthesis, RNA, archaeal, RNA, bacterial, RNA, transfer, amino acyl, RNA, transfer, cys, sulfur/metabolism, biochemistry, bioinformatics, cysteine biosynthesis, genetic code, translation Published in DiRROS: 07.05.2020; Views: 1949; Downloads: 1417
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