title: Inhibition of integrin α2β1 ameliorates glomerular injury.
abstract: Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria.
authors.affiliation: Departments of Medicine and Cancer Biology, Division of Nephrology and Hypertension, Vanderbilt University, Medical Center North, Nashville, TN 37232, USA.
authors.forename: Corina M
authors.initials: CM
authors.lastname: Borza
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.forename: Xiwu
authors.initials: X
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.forename: Stacey
authors.initials: S
authors.lastname: Mont
authors.forename: Sergei
authors.initials: S
authors.lastname: Chetyrkin
authors.forename: Paul
authors.initials: P
authors.lastname: Voziyan
authors.forename: Billy G
authors.initials: BG
authors.lastname: Hudson
authors.forename: Paul C
authors.initials: PC
authors.lastname: Billings
authors.forename: Hyunil
authors.initials: H
authors.lastname: Jo
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bennett
authors.forename: William F
authors.initials: WF
authors.lastname: Degrado
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.forename: Ambra
authors.initials: A
authors.lastname: Pozzi
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology*; D000419:Albuminuria / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D038982:Integrin alpha2beta1 / Q000187:drug effects / Q000378:metabolism*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011897:Random Allocation; D038981:Receptors, Collagen / Q000378:metabolism
chemical_list: D038982:Integrin alpha2beta1; D038981:Receptors, Collagen; D004317:Doxorubicin