Faculty Opinions recommendation of Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis.

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

Download Full-text

Overexpression of Hyaluronan Synthase 2 Alters Hyaluronan Distribution and Function in Proximal Tubular Epithelial Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.2005080879 ◽

2006 ◽

Vol 17 (6) ◽

pp. 1553-1567 ◽

Cited By ~ 37

Author(s):

Wisam Selbi ◽

Anthony J. Day ◽

Marilyn S. Rugg ◽

Csaba Fülöp ◽

Carol A. de la Motte ◽

...

Keyword(s):

Epithelial Cells ◽

Hyaluronan Synthase ◽

Tubular Epithelial Cells ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular ◽

And Function ◽

Hyaluronan Synthase 2

Download Full-text

Overexpression of Hyaluronan Synthase-2 Reduces the Tumorigenic Potential of Glioma Cells Lacking Hyaluronidase Activity

Neurosurgery ◽

10.1097/00006123-200206000-00023 ◽

2002 ◽

Vol 50 (6) ◽

pp. 1311-1318 ◽

Cited By ~ 9

Author(s):

Bouchra Enegd ◽

James A.J. King ◽

Stan Stylli ◽

Lucy Paradiso ◽

Andrew H. Kaye ◽

...

Keyword(s):

Glioma Cells ◽

Hyaluronan Synthase ◽

Hyaluronidase Activity ◽

Tumorigenic Potential ◽

Hyaluronan Synthase 2

Download Full-text

Differences in human placental mesenchymal stromal cells may impair vascular function in FGR

Reproduction ◽

10.1530/rep-21-0226 ◽

2021 ◽

Author(s):

Anna L Boss ◽

Lawrence W Chamley ◽

Anna E.s Brooks ◽

Joanna L James

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Vascular Function ◽

Vascular Dysfunction ◽

Hyaluronan Synthase ◽

Perivascular Niche ◽

Affymetrix Microarrays ◽

Formation Function ◽

Hyaluronan Synthase 2 ◽

And Control

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.

Download Full-text