title: CXCL16 Deficiency Attenuates Renal Injury and Fibrosis in Salt-Sensitive Hypertension.
abstract: Inflammation plays an important role in the pathogenesis of hypertensive kidney disease. However, the molecular mechanisms underlying the induction of inflammation are not completely understood. We have found that CXCL16 is induced in the kidney in deoxycorticosterone acetate (DOCA)-salt hypertension. Here we examined whether CXCL16 is involved in DOCA-salt-induced renal inflammation and fibrosis. Wild-type and CXCL16 knockout mice were subjected to uninephrectomy and DOCA-salt treatment for 3 weeks. There was no difference in blood pressure at baseline between wild-type and CXCL16 knockout mice. DOCA-salt treatment resulted in significant elevation in blood pressure that was comparable between wild-type and CXCL16 knockout mice. CXCL16 knockout mice exhibited less severe renal dysfunction, proteinuria, and fibrosis after DOCA-salt treatment compared with wild-type mice. CXCL16 deficiency attenuated extracellular matrix protein production and suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidneys following DOCA-salt treatment. Furthermore, CXCL16 deficiency reduced macrophage and T cell infiltration into the kidneys in response to DOCA-salt hypertension. Taken together, our results indicate that CXCL16 plays a key role in the pathogenesis of renal injury and fibrosis in salt-sensitive hypertension through regulation of bone marrow-derived fibroblast accumulation and macrophage and T cell infiltration.
authors.affiliation: Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Department of Anesthesiology, Affiliated Foshan Hospital of Sun Yat-sen University, Foshan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Section of Nephrology, Department of Medicine, Shuguang Hospital, Shanghai, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Section of Nephrology, Department of Internal Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Section of Nephrology, Department of Medicine, Shuguang Hospital, Shanghai, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.affiliation: Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.|Center for Translational Research on Inflammatory Diseases (CTRID) and Renal Section, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D000075743:Chemokine CXCL16 / Q000172:deficiency*; D003900:Desoxycorticosterone / Q000009:adverse effects* / Q000494:pharmacology; D005355:Fibrosis; D006977:Hypertension, Renal / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000075743:Chemokine CXCL16; C498926:Cxcl16 protein, mouse; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone