title: Serum miRNA-122 in acute liver injury induced by kidney injury and sepsis in CD-1 mouse models.
abstract: OBJECTIVE
  miRNA-122 (miR-122) is a new, interesting liver injury biomarker but little is known about its effects when there is an indirect acute liver injury.
  
  
  METHODS
  We investigated this by using indirect liver injury mice models with bilateral ureter obstruction (BUO), bilateral nephrectomy (BiNx) and cecal ligation and puncture (CLP). A direct liver injury model, liver ischemia/reperfusion injury (liver I/R), was performed in parallel. Liver injury (i.e. liver histology, alanine transaminase [ALT]), kidney damage (i.e. serum creatinine) and cytokines (i.e. tumor necrosis factor-α, interleukin [IL]-6, IL-1β, IL-10) were assessed.
  
  
  RESULTS
  Six hours after BUO/BiNx/CLP, the ALT and serum cytokines were approximately 1.5-fold higher than the baseline whereas miR-122 did not change. After 6 h of BiNx, there were prominent hepatocyte vacuolization but no elevations of miR-122. However, after 24 h of BUO/BiNx/CLP, ALT, hepatocyte vacuolization and miR-122 increased. The cytokines at 6 h might have induced the production of miR-122 at 24 h. The results from the in vitro study with HepG2 cells and each of the cytokines resulted in increased miR-122. On the other hand, when the direct liver injury model was used, there was a fivefold and 22-fold increase in the ALT at 0.5 and 1 h after surgery, respectively, and high serum miR-122 which corroborated the results from the liver histopathology.
  
  
  CONCLUSIONS
  We demonstrated that prior serum cytokine accumulation increased serum miR-122 in indirect liver injury induced by BUO/BiNx and less severe sepsis mouse models. Cytokine accumulation may be responsible for miR-122 expression in these models. The clinical importance of liver injury demonstrated by the discordance between serum miR-122 and ALT was an interesting issue.
authors: Immunology Unit, Department of Microbiology, Bangkok, Thailand.|Division of Nephrology, Department of Medicine, Bangkok, Thailand.
authors: Asada
authors: A
authors: Leelahavanichkul
authors: Research Affairs, Bangkok, Thailand.
authors: Poorichaya
authors: P
authors: Somparn
authors: Immunology Unit, Department of Microbiology, Bangkok, Thailand.
authors: Thanaporn
authors: T
authors: Panich
authors: Division of Nephrology, Department of Medicine, Bangkok, Thailand.|Chakri Naruebodindra Medical Institute (CNMI), Faculty of Medicine Ramathibody Hospital, Mahidol University, Bangkok, Thailand.
authors: Wiwat
authors: W
authors: Chancharoenthana
authors: Department of Pathology, Bangkok, Thailand.
authors: Jutamas
authors: J
authors: Wongphom
authors: Research Affairs, Bangkok, Thailand.
authors: Trairak
authors: T
authors: Pisitkun
authors: Immunology Unit, Department of Microbiology, Bangkok, Thailand.|Center of Excellence in Immunology and Immune-Mediated Diseases, Bangkok, Thailand.
authors: Nattiya
authors: N
authors: Hirankarn
authors: Division of Nephrology, Department of Medicine, Bangkok, Thailand.
authors: Somchai
authors: S
authors: Eiam-Ong
keywords: acute kidney injury-induced liver injury; miR-122; sepsis-induced liver injury