Open AccessInhibition of apoptosis signal-regulating kinase 1 mitigates the pathogenesis of human immunodeficiency virus-associated nephropathy
Author(s) -
Anqun Chen,
Jianing Xu,
Han Lai,
Vivette D. D’Agati,
Tianjun Guan,
Shawn S. Badal,
John T. Liles,
John Cijiang He,
Kyung Hwa Lee
Publication year - 2020
Publication title -
nephrology, dialysis, transplantation/nephrology dialysis transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.654
H-Index - 168
eISSN - 1460-2385
pISSN - 0931-0509
DOI - 10.1093/ndt/gfaa198
Subject(s) - medicine , nephropathy , kidney disease , glomerulosclerosis , kidney , renal function , immunology , focal segmental glomerulosclerosis , endocrinology , cancer research , glomerulonephritis , proteinuria , diabetes mellitus
Chronic kidney disease (CKD) is a common cause of morbidity and mortality in human immunodeficiency virus (HIV)-positive individuals. Among the HIV-related kidney diseases, HIV-associated nephropathy (HIVAN) is a rapidly progressive renal disease characterized by collapsing focal glomerulosclerosis (GS), microcystic tubular dilation, interstitial inflammation and fibrosis. Although the incidence of end-stage renal disease due to HIVAN has dramatically decreased with the widespread use of antiretroviral therapy, the prevalence of CKD continues to increase in HIV-positive individuals. Recent studies have highlighted the role of apoptosis signal-regulating kinase 1 (ASK1) in driving kidney disease progression through the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase and selective ASK-1 inhibitor GS-444217 was recently shown to reduce kidney injury and disease progression in various experimental models. Therefore we examined the efficacy of ASK1 antagonism by GS-444217 in the attenuation of HIVAN in Tg26 mice.