Parathyroid Hormone–Related Protein Contributes to Early Healing of Habu Snake Venom–Induced Glomerulonephritis in Mice
Autor: | Denis Raison, Mazène Hochane, Thierry Massfelder, Sabrina Danilin, Audrey Bethry, Catherine Coquard, Claire Béraud, Mariette Barthelmebs |
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Přispěvatelé: | Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), univOAK, Archive ouverte |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty medicine.medical_treatment Kidney Glomerulus 030232 urology & nephrology Inflammation [SDV.CAN]Life Sciences [q-bio]/Cancer Injections Pathology and Forensic Medicine Proinflammatory cytokine 03 medical and health sciences Glomerulonephritis 0302 clinical medicine [SDV.CAN] Life Sciences [q-bio]/Cancer Internal medicine Crotalid Venoms medicine Animals Trimeresurus Cell Proliferation Mesangial cell Parathyroid hormone-related protein business.industry Growth factor Parathyroid Hormone-Related Protein medicine.disease Antibodies Neutralizing Mice Inbred C57BL 030104 developmental biology Endocrinology Snake venom Creatinine Mesangial proliferative glomerulonephritis medicine.symptom business hormones hormone substitutes and hormone antagonists |
Zdroj: | American Journal of Pathology American Journal of Pathology, 2018, 188 (4), pp.863-875. ⟨10.1016/j.ajpath.2017.12.012⟩ |
ISSN: | 0002-9440 1525-2191 |
DOI: | 10.1016/j.ajpath.2017.12.012⟩ |
Popis: | International audience; Proliferative glomerulonephritis is characterized by local inflammation and mesangial cell deterioration, followed by mesangial proliferation and glomerular healing. Parathyroid hormone-related peptide (PTHrP) is a mesangial cytokine-like growth factor implicated in mesangial proliferation and survival. No data are available about its role in glomerulonephritis. Herein, we analyzed the expression and role of PTHrP in glomerular inflammation and healing in an experimental model of glomerulonephritis induced by i.v. injection of Habu snake venom in mice. The temporal analysis showed marked renal damage in the first days after venom injection and the beginning of recovery within 7 days. Glomerular expression of PTHrP (transcript and protein) was observed in the early phase after venom injection (from day 1 to day 3), along with an inflammatory environment. The inactivation of secreted PTHrP with PTHrP-neutralizing antibody (PTH2E11; 120 μg i.p. daily) reduced the markers of local inflammation (expression of macrophage chemotactic protein-1; regulated upon activation, normal T cell expressed and secreted; cyclooxygenase 2; IL-6; and macrophage infiltration) and abolished the expression of PTHrP itself. Moreover, the glomerular cell proliferation was hampered, and the healing process was prevented on day 7 after venom injection. These results show that PTHrP has antinomic actions in glomerulonephritis, participating in both the proinflammatory condition and the healing process. Our work reveals the essential role of PTHrP in early glomerular repair in an experimental model of glomerulonephritis. |
Databáze: | OpenAIRE |
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