Fibrosis　is　a　pathological　feature　of　chronic　kidney　disease　and　its　progression　correlates　with　declining　renal　function.　Kidney　fibrosis　is　driven　by　multiple　profibrotic　factors.　This　project　examined　the　regulatory　function　of　WNT1-inducible-signaling　pathway　protein　1　(WISP1)　in　the　development　of　kidney　fibrosis.　Induction　of　WISP1　by　transforming　growth　factor　beta　1　(TGF-beta　1),　and　the　role　of　WISP1　in　TGF-beta　1/Smad　signaling　and　fibrotic　responses,　was　examined　in　multiple　kidney　cells.　Kidney　expression　of　WISP1　was　examined　in　mouse　models　of　unilateral　ureter　obstruction　(UUO)　and　streptozotocin-induced　diabetic　nephropathy.　WISP1　antibody　was　administered　to　UUO　mice　during　the　induction　of　kidney　injury　and　the　impact　on　kidney　fibrosis　was　examined.　WISP1　expression　was　upregulated　in　both　mouse　models.　TGF-beta　1-induced　expression　of　WISP1　and　profibrotic　genes　in　cultured　kidney　cells　via　TGF-beta　R1.　Recombinant　WISP1-induced　expression　of　TGF-beta　R1　in　kidney　cells.　Suppression　of　WISP1　by　shRNA　or　neutralizing　antibody　reduced　TGF-beta　1-mediated　activation　of　Smad3,　fibrotic　gene　expression,　and　fibroblast　proliferation.　Treatment　with　WISP1　antibody　inhibited　the　development　of　kidney　fibrosis　in　UUO　mice.　WISP1　mediates　the　profibrotic　effects　of　TGF-beta　1　in　kidney　cells　and　in　kidney　disease.　Pharmacological　blockade　of　WISP1　exhibits　potential　as　a　novel　therapy　for　inhibiting　kidney　fibrosis.