title: Lack of hyaluronidases exacerbates renal post-ischemic injury, inflammation, and fibrosis.
abstract: Renal ischemia-reperfusion injury (IRI) is a pathological process that may lead to acute renal failure and chronic dysfunction in renal allografts. During IRI, hyaluronan (HA) accumulates in the kidney, but suppression of HA accumulation during IRI protects the kidney from ischemic insults. Here we tested whether Hyal1-/- and Hyal2-/- mice display exacerbated renal damage following unilateral IRI due to a higher HA accumulation in the post-ischemic kidney compared with that in the kidney of wild-type mice. Two days after IRI in male mice there was accumulation of HA and CD44 in the kidney, marked tubular damage, infiltration, and increase creatininemia in wild-type mice. Knockout mice exhibited higher amounts of HA and higher creatininemia. Seven days after injury, wild-type mice had a significant decrease in renal damage, but knockout mice still displayed exacerbated inflammation. HA and CD44 together with α-smooth muscle actin and collagen types I and III expression were increased in knockout compared with wild-type mice 30 days after IRI. Thus, both HA-degrading enzymes seem to be protective against IRI most likely by reducing HA accumulation in the post-ischemic kidney and decreasing the inflammatory processes. Deficiency in either HYAL1 or HYAL2 leads to enhanced HA accumulation in the post-ischemic kidney and consequently worsened inflammatory response, increased tubular damage, and fibrosis.
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Colombaro
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Inès
authors.initials: I
authors.lastname: Jadot
authors.affiliation: 1] Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium [2] Laboratory of Experimental Nephrology, Université Libre de Bruxelles-ULB, Brussels, Belgium.
authors.forename: Anne-Emilie
authors.initials: AE
authors.lastname: Declèves
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Voisin
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Giordano
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Habsch
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Malaisse
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Flamion
authors.affiliation: Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Caron
mesh_terms: D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005355:Fibrosis; D058851:GPI-Linked Proteins / Q000235:genetics; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000172:deficiency* / Q000235:genetics; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009083:Mucopolysaccharidoses / Q000150:complications* / Q000235:genetics; D009393:Nephritis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009504:Neutrophils; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism
chemical_list: D000199:Actins; C491768:Ccl2 protein, mouse; C476399:Cd44 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D024042:Collagen Type I; D024061:Collagen Type III; C404915:Cxcl2 protein, mouse; D058851:GPI-Linked Proteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; C544013:alpha-smooth muscle actin, mouse; D006820:Hyaluronic Acid; D003404:Creatinine; C469220:Hyal1 protein, mouse; C469221:Hyal2 protein, mouse; D006821:Hyaluronoglucosaminidase