title: Role of Axl in early kidney inflammation and progression of salt-dependent hypertension.
abstract: The Gas6/Axl pathway regulates many cell functions and is implicated in hypertension. In this study, we aimed to investigate the role of Axl in immune cells on initiation and progression of salt-dependent hypertension. Deoxycorticosterone acetate (75 mg/60 days release)-salt hypertension was induced for 1 week or 6 weeks in Axl chimeras generated by bone marrow transplant to restrict Axl deficiency to hematopoietic or nonhematopoietic compartments. Depletion of Axl in hematopoietic cells (Axl(-/-) →Axl(+/+)) reduced (133 ± 2 mm Hg) increase in systolic blood pressure compared with other Axl chimeras (≈150 mm Hg) 1 week after deoxycorticosterone acetate-salt. Urine protein and renal oxidative stress were lowest in Axl(-/-) →Axl(+/+) at 1 week after deoxycorticosterone acetate-salt. Compensatory increase in Gas6 in kidneys of recipient Axl(-/-) may affect kidney function and blood pressure in early phase of hypertension. Flow cytometry on kidneys from Axl(-/-) →Axl(+/+) showed increase in total leukocytes, B, and dendritic cells and decrease in macrophages compared with Axl(+/+) →Axl(+/+). These immune changes were associated with decrease in proinflammatory gene expression, in particular interferon γ. Systolic blood pressure returned to baseline in Axl(-/-) →Axl(+/+) and Axl(-/-) →Axl(-/-) but remained increased in Axl(+/+) →Axl(+/+) and Axl(+/+) →Axl(-/-) chimeras after 6 weeks of deoxycorticosterone acetate-salt. Vascular apoptosis was increased in the global Axl(-/-) chimeras in the late phase of hypertension. In summary, we found that expression of Axl in hematopoietic cells is critical for kidney pathology in early phase of salt-dependent hypertension. However, Axl in both hematopoietic and nonhematopoietic lineages contributes to the late phase of hypertension.
authors.affiliation: Department of Medicine and Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Sri N
authors.initials: SN
authors.lastname: Batchu
authors.forename: Angie
authors.initials: A
authors.lastname: Hughson
authors.forename: Janice
authors.initials: J
authors.lastname: Gerloff
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Fowell
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Korshunov
mesh_terms: D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D003900:Desoxycorticosterone / Q000494:pharmacology*; D018450:Disease Progression; D006973:Hypertension / Q000150:complications* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D009393:Nephritis / Q000209:etiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D018925:Chemokines; D016207:Cytokines; D003900:Desoxycorticosterone; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722290:AXL receptor tyrosine kinase, mouse
keywords: Axl receptor tyrosine kinase; bone marrow transplantation; hypertension; immunity; kidney