BACKGROUND: The turnover of hyaluronan (HA), especially the production of low-molecular-weight fragments of HA, was examined in a model of unilateral renal ischaemia-reperfusion (IR) in rats. METHODS: HA was extracted from the outer and inner stripe of the outer medulla (OSOM and ISOM) at different times following IR. Its fragmentation was measured using membrane filtration and size-exclusion chromatography. Quantitative reverse transcription-polymerase chain reaction, zymography and immunohistochemistry were used to assess the expression and localization of various forms of HA synthase (HAS) and hyaluronidase (HYAL). Macrophage infiltration was evaluated using immunohistochemistry. RESULTS: HA accumulated at Day 1 mostly as high-molecular-weight (HMW) species with an elution profile similar to a reference 2500 kDa HA and at Day 14 mostly as medium- to low-size fragments. Within 1 day, HAS1 messenger RNA was up-regulated > 50- and 35-fold in OSOM and ISOM, respectively. Thereafter, HAS1 tended to normalize, while HAS2 increased steadily. Both synthetic enzymes were localized around tubules and in the interstitium. Conversely, HYAL1, HYAL2 and global hyaluronidase activity were repressed during the first 24 h. The patterns were identical in the OSOM and ISOM despite markedly different amounts of HA at baseline. There was no obvious correlation between HA deposits and macrophage infiltration. CONCLUSIONS: In the post-ischaemic kidney, HA starts to accumulate at Day 1 mostly as HMW species. Later on, a large proportion becomes degraded into smaller fragments. This pattern is explained by coordinated changes in the expression of HA synthases and hyaluronidases, especially an early induction of HAS1. The current data open the door to timed pharmacological interventions blocking the production of HA fragments.
BACKGROUND: The turnover of hyaluronan (HA), especially the production of low-molecular-weight fragments of HA, was examined in a model of unilateral renal ischaemia-reperfusion (IR) in rats. METHODS:HA was extracted from the outer and inner stripe of the outer medulla (OSOM and ISOM) at different times following IR. Its fragmentation was measured using membrane filtration and size-exclusion chromatography. Quantitative reverse transcription-polymerase chain reaction, zymography and immunohistochemistry were used to assess the expression and localization of various forms of HA synthase (HAS) and hyaluronidase (HYAL). Macrophage infiltration was evaluated using immunohistochemistry. RESULTS:HA accumulated at Day 1 mostly as high-molecular-weight (HMW) species with an elution profile similar to a reference 2500 kDa HA and at Day 14 mostly as medium- to low-size fragments. Within 1 day, HAS1 messenger RNA was up-regulated > 50- and 35-fold in OSOM and ISOM, respectively. Thereafter, HAS1 tended to normalize, while HAS2 increased steadily. Both synthetic enzymes were localized around tubules and in the interstitium. Conversely, HYAL1, HYAL2 and global hyaluronidase activity were repressed during the first 24 h. The patterns were identical in the OSOM and ISOM despite markedly different amounts of HA at baseline. There was no obvious correlation between HA deposits and macrophage infiltration. CONCLUSIONS: In the post-ischaemic kidney, HA starts to accumulate at Day 1 mostly as HMW species. Later on, a large proportion becomes degraded into smaller fragments. This pattern is explained by coordinated changes in the expression of HA synthases and hyaluronidases, especially an early induction of HAS1. The current data open the door to timed pharmacological interventions blocking the production of HA fragments.
Authors: Eric P Schmidt; Katherine H Overdier; Xiaojun Sun; Lei Lin; Xinyue Liu; Yimu Yang; Lee Anne Ammons; Terra D Hiller; Matt A Suflita; Yanlei Yu; Yin Chen; Fuming Zhang; Clay Cothren Burlew; Charles L Edelstein; Ivor S Douglas; Robert J Linhardt Journal: Am J Respir Crit Care Med Date: 2016-08-15 Impact factor: 21.405
Authors: Geneviève Bart; Nuria Ortega Vico; Antti Hassinen; Francois M Pujol; Ashik Jawahar Deen; Aino Ruusala; Raija H Tammi; Anthony Squire; Paraskevi Heldin; Sakari Kellokumpu; Markku I Tammi Journal: J Biol Chem Date: 2015-03-20 Impact factor: 5.157
Authors: Thomas Baudoux; Inès Jadot; Anne-Emilie Declèves; Marie-Hélène Antoine; Jean-Marie Colet; Olivia Botton; Eric De Prez; Agnieszka Pozdzik; Cécile Husson; Nathalie Caron; Joëlle L Nortier Journal: Front Med (Lausanne) Date: 2022-05-04
Authors: Xinyi Wang; Swathi Balaji; Emily H Steen; Alexander J Blum; Hui Li; Christina K Chan; Scott R Manson; Thomas C Lu; Meredith M Rae; Paul F Austin; Thomas N Wight; Paul L Bollyky; Jizhong Cheng; Sundeep G Keswani Journal: JCI Insight Date: 2020-06-18