Microcystin exposure worsens nonalcoholic fatty liver disease associated ectopic glomerular toxicity via nox-2-mir21 axis

Publication date: Available online 20 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Sutapa Sarkar, Firas Alhasson, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Shuo Xiao, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh ChatterjeeAbstractNAFLD often results in cardiovascular, intestinal and renal complications. Previous reports from our laboratory highlighted NAFLD induced ectopic inflammatory manifestations in the kidney that gave rise to glomerular inflammation. Extending our studies, we hypothesized that existing inflammatory conditions in NAFLD could make the kidneys more susceptible to environmental toxicity. Our results showed that exposure of Microcystin-LR (MC) in NAFLD mice caused a marked increase in cellular scarring with a concomitant increase in mesangial cell activation as observed by increased α-SMA in the extracellular matrix surrounding the glomeruli. Renal tissue surrounding the glomeruli also showed increased NOX2 activation as shown by greater co-localization of p47 Phox and its membrane component gp91Phox both in the mesangial cell and surrounding tissue. Mechanistically, mesangial cells incubated with apocynin, nitrone spin trap DMPO and miR21 inhibitor showed significantly decreased α-SMA, miR21 levels and proinflammatory cytokine release in the supernatant. In parallel, mice lacking miR21, known to be activated by NOX2, when exposed to MC in NAFLD showed decreased mesangial c...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research