Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease]
Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte
The American Society for Biochemistry and Molecular Biology (ASBMB)
Published 2018
The American Society for Biochemistry and Molecular Biology (ASBMB)
Published 2018
| Publication Date: |
2018-01-13
|
|---|---|
| Publisher: |
The American Society for Biochemistry and Molecular Biology (ASBMB)
|
| Print ISSN: |
0021-9258
|
| Electronic ISSN: |
1083-351X
|
| Topics: |
Biology
Chemistry and Pharmacology
|
| Published by: |
| _version_ | 1836398749032644608 |
|---|---|
| autor | Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte |
| beschreibung | We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel “bed of nails”-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses. |
| citation_standardnr | 6138311 |
| datenlieferant | ipn_articles |
| feed_id | 43 |
| feed_publisher | The American Society for Biochemistry and Molecular Biology (ASBMB) |
| feed_publisher_url | http://www.asbmb.org/ |
| insertion_date | 2018-01-13 |
| journaleissn | 1083-351X |
| journalissn | 0021-9258 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Biochemistry and Molecular Biology (ASBMB) |
| quelle | Journal of Biological Chemistry |
| relation | http://feedproxy.google.com/~r/jbc/SUcv/~3/3WhQTystFGs/567.short |
| search_space | articles |
| shingle_author_1 | Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte |
| shingle_author_2 | Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte |
| shingle_author_3 | Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte |
| shingle_author_4 | Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte |
| shingle_catch_all_1 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel “bed of nails”-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses. Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_2 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel “bed of nails”-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses. Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_3 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel “bed of nails”-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses. Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_catch_all_4 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. We recently reported that insulitis in type 1 diabetes of mice and humans is preceded by intraislet accumulation of HA, a highly hygroscopic polymer. Using the double transgenic DO11.10 × RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked whether autoimmune insulitis was associated with changes in the stiffness of islets. To measure islet stiffness, we used atomic force microscopy (AFM) and developed a novel “bed of nails”-like approach that uses quartz glass nanopillars to anchor islets, solving a long-standing problem of keeping tissue-scale objects immobilized while performing AFM. We measured stiffness via AFM nanoindentation with a spherical indenter and found that insulitis made islets mechanically soft compared with controls. Conversely, treatment with 4-methylumbelliferone, a small-molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling, and restored basal tissue stiffness. These results indicate that HA content governs the mechanical properties of islets. In hydrogels with variable HA content, we confirmed that increased HA leads to mechanically softer hydrogels, consistent with our model. In light of recent reports that the insulin production of islets is mechanosensitive, these findings open up an exciting new avenue of research into the fundamental mechanisms by which inflammation impacts local cellular responses. Nadine Nagy, Adi de la Zerda, Gernot Kaber, Pamela Y. Johnson, Kenneth H. Hu, Michael J. Kratochvil, Koshika Yadava, Wenting Zhao, Yi Cui, Guadalupe Navarro, Justin P. Annes, Thomas N. Wight, Sarah C. Heilshorn, Paul L. Bollyky, Manish J. Butte The American Society for Biochemistry and Molecular Biology (ASBMB) 0021-9258 00219258 1083-351X 1083351X |
| shingle_title_1 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| shingle_title_2 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| shingle_title_3 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| shingle_title_4 | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| timestamp | 2025-06-30T23:32:01.487Z |
| titel | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| titel_suche | Hyaluronan content governs tissue stiffness in pancreatic islet inflammation [Molecular Bases of Disease] |
| topic | W V |
| uid | ipn_articles_6138311 |