scholarly journals Changed lamellipodial extension, adhesion plaques and migration in epidermal keratinocytes containing constitutively expressed sense and antisense hyaluronan synthase 2 (Has2) genes

2002 ◽  
Vol 115 (18) ◽  
pp. 3633-3643 ◽  
Author(s):  
K. Rilla
Hyaluronan ◽  
2002 ◽  
pp. 557-560
Author(s):  
Kirsi Rilla ◽  
Mikko Lammi ◽  
Reijo Sironen ◽  
Vincent C. Hascall ◽  
Ronald Midura ◽  
...  

2018 ◽  
Vol 475 (10) ◽  
pp. 1755-1772 ◽  
Author(s):  
Leena Rauhala ◽  
Tiina Jokela ◽  
Riikka Kärnä ◽  
Geneviève Bart ◽  
Piia Takabe ◽  
...  

Extracellular nucleotides are used as signaling molecules by several cell types. In epidermis, their release is triggered by insults such as ultraviolet radiation, barrier disruption, and tissue wounding, and by specific nerve terminals firing. Increased synthesis of hyaluronan, a ubiquitous extracellular matrix glycosaminoglycan, also occurs in response to stress, leading to the attractive hypothesis that nucleotide signaling and hyaluronan synthesis could also be linked. In HaCaT keratinocytes, ATP caused a rapid and strong but transient activation of hyaluronan synthase 2 (HAS2) expression via protein kinase C-, Ca2+/calmodulin-dependent protein kinase II-, mitogen-activated protein kinase-, and calcium response element-binding protein-dependent pathways by activating the purinergic P2Y2 receptor. Smaller but more persistent up-regulation of HAS3 and CD44, and delayed up-regulation of HAS1 were also observed. Accumulation of peri- and extracellular hyaluronan followed 4–6 h after stimulation, an effect further enhanced by the hyaluronan precursor glucosamine. AMP and adenosine, the degradation products of ATP, markedly inhibited HAS2 expression and, despite concomitant up-regulation of HAS1 and HAS3, inhibited hyaluronan synthesis. Functionally, ATP moderately increased cell migration, whereas AMP and adenosine had no effect. Our data highlight the strong influence of adenosinergic signaling on hyaluronan metabolism in human keratinocytes. Epidermal insults are associated with extracellular ATP release, as well as rapid up-regulation of HAS2/3, CD44, and hyaluronan synthesis, and we show here that the two phenomena are linked. Furthermore, as ATP is rapidly degraded, the opposite effects of its less phosphorylated derivatives facilitate a rapid shut-off of the hyaluronan response, providing a feedback mechanism to prevent excessive reactions when more persistent signals are absent.


2001 ◽  
Vol 276 (23) ◽  
pp. 20428-20435 ◽  
Author(s):  
Juha-Pekka Pienimäki ◽  
Kirsi Rilla ◽  
Csaba Fülöp ◽  
Reijo K. Sironen ◽  
Susanna Karvinen ◽  
...  

Author(s):  
HAKAN AKGUN ◽  
Selma Metintas ◽  
Guntulu Ak ◽  
Secil Demirkol ◽  
Murat Isbilen ◽  
...  

IntroductionThe prognosis of malignant pleural mesothelioma (MPM) is poor with a limited survival time. In this study, we aimed to examine expression levels of genes selected from relevant literature and to utilize in silico methods to determine genes whose expression could reflect the prognosis of the patients with MPM by ex-vivo validation experimentsMaterial and methodsThe study group consisted of 54 MPM patients treated by chemotherapy. Expression of 6 genes; midkine (MDK), syndecan 1 (SDC1), hyaluronan synthase 2 (HAS2), sestrin 1 (SESN1), laminin subunit alpha 4 (LAMA4), and fibulin 3 (FBLN3) were examined by qPCR in tumor tissues. SESN1 and LAMA4 were identified using an in house R-based script “Unsupervised Survival Analysis Tool." MDK, SDC1, HAS2, and FBLN3 were selected from current literature. We used two housekeeping genes; glucose-6-phosphate dehydrogenase and TATA-box binding protein as controls.ResultsOf the patients, 43 (79.6%) had epithelioid mesothelioma. The median survival for all patients was 10 (±1.2 SE) months (CI 95%; 7.7-12.3). In multivariate analyses, MDK (p=0.007), HAS2 (p=0.008) and SESN1 (p=0.014) expression were related with survival time in whole group. In epithelioid type MPM patients, MDK (p=0.014), FBLN3 (p=0.029), HAS2 (p=0.014) and SESN1 (p=0.045) expression was related with survival time by multivariate analyses.ConclusionsHigh HAS2 and SESN1 expressions and low MDK are potential biomarkers of good prognosis in MPM. High HAS2 and SESN1 expression and low MDK and FBLN3 can also be utilized as biomarkers of good prognosis for epithelioid MPM. Those results should be further investigated in sera, plasma, and pleural effusions


2006 ◽  
Vol 17 (6) ◽  
pp. 1553-1567 ◽  
Author(s):  
Wisam Selbi ◽  
Anthony J. Day ◽  
Marilyn S. Rugg ◽  
Csaba Fülöp ◽  
Carol A. de la Motte ◽  
...  

Neurosurgery ◽  
2002 ◽  
Vol 50 (6) ◽  
pp. 1311-1318 ◽  
Author(s):  
Bouchra Enegd ◽  
James A.J. King ◽  
Stan Stylli ◽  
Lucy Paradiso ◽  
Andrew H. Kaye ◽  
...  

Reproduction ◽  
2021 ◽  
Author(s):  
Anna L Boss ◽  
Lawrence W Chamley ◽  
Anna E.s Brooks ◽  
Joanna L James

Placentae from pregnancies with fetal growth restriction (FGR) exhibit poor oxygen and nutrient exchange, in part due to impaired placental vascular development. Placental mesenchymal stromal cells (pMSCs) reside in a perivascular niche, where they may influence blood vessel formation/ function. However, the role of pMSCs in vascular dysfunction in FGR is unclear. To elucidate the mechanisms by which pMSCs may impact placental vascularisation we compared the transcriptomes of human pMSCs isolated from FGR (<5th centile) (n=7) and gestation-matched control placentae (n=9) using Affymetrix microarrays. At the transcriptome level there were no statistically significant differences between normal and FGR pMSCs, however several genes linked to vascular function exhibited notable fold changes, and thus the dataset was used as a hypothesis-generating tool for possible dysfunction in FGR. Genes/proteins of interest were followed up by real-time PCR and by immunohistochemistry. Gene expression of ADAMTS1 and FBLN2 (fibulin-2) were significantly upregulated, whilst HAS2 (hyaluronan synthase-2) was significantly downregulated, in pMSCs from FGR placentae (n=8) relative to controls (n=7, p<0.05 for all). At the protein level, significant differences in the level of fibulin-2 and hyaluronan synthase-2, but not ADAMTS1 were confirmed between pMSCs from FGR and control pregnancies by western blot. All three proteins demonstrated perivascular expression in third-trimester placentae. Fibulin-2 maintains vessel elasticity, and its increased expression in FGR pMSCs could help explain the increased distensibility of FGR blood vessels. ADAMTS1 and hyaluronan synthase-2 regulate angiogenesis, and their differential expression by FGR pMSCs may contribute to the impaired angiogenesis in these placentae.


Endocrinology ◽  
2002 ◽  
Vol 143 (11) ◽  
pp. 4375-4384 ◽  
Author(s):  
Angelika E. Stock ◽  
Nadine Bouchard ◽  
Kristy Brown ◽  
Andrew P. Spicer ◽  
Charles B. Underhill ◽  
...  

2006 ◽  
Vol 281 (26) ◽  
pp. 18043-18050 ◽  
Author(s):  
Jamie Monslow ◽  
John D. Williams ◽  
Donald J. Fraser ◽  
Daryn R. Michael ◽  
Pelagia Foka ◽  
...  

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