Abundance and size of hyaluronan in naked mole-rat tissues and plasma

Abstract Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins....

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Autores principales: Delphine del Marmol, Susanne Holtze, Nadia Kichler, Arne Sahm, Benoit Bihin, Virginie Bourguignon, Sophie Dogné, Karol Szafranski, Thomas Bernd Hildebrandt, Bruno Flamion
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/d7085e041e044033971449e3ea7d50e2
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spelling oai:doaj.org-article:d7085e041e044033971449e3ea7d50e22021-12-02T14:26:12ZAbundance and size of hyaluronan in naked mole-rat tissues and plasma10.1038/s41598-021-86967-92045-2322https://doaj.org/article/d7085e041e044033971449e3ea7d50e22021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86967-9https://doaj.org/toc/2045-2322Abstract Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins. Its molecular weight was determined using size exclusion chromatography and gel electrophoresis, HA family gene expression using RNAseq analysis, and hyaluronidase activity using zymography. Guinea pigs (Cavia porcellus) and mice (Mus musculus) were used as controls for some experiments. We found that HA localization was similar in NMR, guinea pig, and mouse tissues but NMR had larger amounts and higher molecular weight (maximum, around 2.5 MDa) of HA in serum and almost all tissues tested. We could not find ultra-high molecular weight HA (≥ 4 MDa) in NMR samples, in contrast to previous descriptions. Hyaluronidase-1 had lower expression and activity in NMR than mouse lymph nodes. RNAseq results showed that, among HA family genes, Tnfaip6 and hyaluronidase-3 (Hyal3) were systematically overexpressed in NMR tissues. In conclusion, NMR samples, contrary to expectations, do not harbor ultra-high molecular weight HA, although its amount and average molecular weight are higher in NMR than in guinea pig tissues and serum. Although hyaluronidase expression and activity are lower in NMR than mouse lymph nodes, this not sufficient to explain the presence of high molecular weight HA. A different activity of the NMR HA synthases remains possible. These characteristics, together with extremely high Hyal3 and Tnfaip6 expression, may provide the NMR with a bespoke, and perhaps protective, HA metabolism.Delphine del MarmolSusanne HoltzeNadia KichlerArne SahmBenoit BihinVirginie BourguignonSophie DognéKarol SzafranskiThomas Bernd HildebrandtBruno FlamionNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Delphine del Marmol
Susanne Holtze
Nadia Kichler
Arne Sahm
Benoit Bihin
Virginie Bourguignon
Sophie Dogné
Karol Szafranski
Thomas Bernd Hildebrandt
Bruno Flamion
Abundance and size of hyaluronan in naked mole-rat tissues and plasma
description Abstract Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins. Its molecular weight was determined using size exclusion chromatography and gel electrophoresis, HA family gene expression using RNAseq analysis, and hyaluronidase activity using zymography. Guinea pigs (Cavia porcellus) and mice (Mus musculus) were used as controls for some experiments. We found that HA localization was similar in NMR, guinea pig, and mouse tissues but NMR had larger amounts and higher molecular weight (maximum, around 2.5 MDa) of HA in serum and almost all tissues tested. We could not find ultra-high molecular weight HA (≥ 4 MDa) in NMR samples, in contrast to previous descriptions. Hyaluronidase-1 had lower expression and activity in NMR than mouse lymph nodes. RNAseq results showed that, among HA family genes, Tnfaip6 and hyaluronidase-3 (Hyal3) were systematically overexpressed in NMR tissues. In conclusion, NMR samples, contrary to expectations, do not harbor ultra-high molecular weight HA, although its amount and average molecular weight are higher in NMR than in guinea pig tissues and serum. Although hyaluronidase expression and activity are lower in NMR than mouse lymph nodes, this not sufficient to explain the presence of high molecular weight HA. A different activity of the NMR HA synthases remains possible. These characteristics, together with extremely high Hyal3 and Tnfaip6 expression, may provide the NMR with a bespoke, and perhaps protective, HA metabolism.
format article
author Delphine del Marmol
Susanne Holtze
Nadia Kichler
Arne Sahm
Benoit Bihin
Virginie Bourguignon
Sophie Dogné
Karol Szafranski
Thomas Bernd Hildebrandt
Bruno Flamion
author_facet Delphine del Marmol
Susanne Holtze
Nadia Kichler
Arne Sahm
Benoit Bihin
Virginie Bourguignon
Sophie Dogné
Karol Szafranski
Thomas Bernd Hildebrandt
Bruno Flamion
author_sort Delphine del Marmol
title Abundance and size of hyaluronan in naked mole-rat tissues and plasma
title_short Abundance and size of hyaluronan in naked mole-rat tissues and plasma
title_full Abundance and size of hyaluronan in naked mole-rat tissues and plasma
title_fullStr Abundance and size of hyaluronan in naked mole-rat tissues and plasma
title_full_unstemmed Abundance and size of hyaluronan in naked mole-rat tissues and plasma
title_sort abundance and size of hyaluronan in naked mole-rat tissues and plasma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d7085e041e044033971449e3ea7d50e2
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