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
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