VISTA Confers Renal Protection in Murine Hemorrhage/Infection-Induced Acute Kidney Injury: Associations with Altered NGAL and HMGB1 Expression.

Authors

Yuan Yuan, Lei Fang, Yangliang Yang, Mengzhi Pan, Daoqin Gao, Chuan Geng, Baoji Hu

Published in

ImmunoTargets and therapy. Volume 15. Pages 641577. Epub Sep 29, 2026.

Abstract

Acute kidney injury (AKI) represents a serious complication associated with both short- and long-term morbidity and mortality in critically ill patients. Severe trauma complicated by infection represents a high‑risk clinical trigger for AKI. V‑domain immunoglobulin suppressor of T‑cell activation (VISTA) is an immune‑checkpoint molecule with immunomodulatory functions, yet its role in trauma‑sepsis‑induced AKI remains incompletely defined.
In this experimental study, male wild‑type (WT) and VISTA‑deficient (VISTA^-/-) C57BL/6 mice were utilized to establish a two‑hit murine AKI model combining hemorrhagic shock and cecal ligation and puncture (Hem/CLP). Blood and kidney tissues were collected 24 hours after hemorrhage/CLP. VISTA expression on neutrophils and monocytes in peripheral blood was assessed by flow cytometry. Serum creatinine and blood urea nitrogen were measured according to manufacturer protocols. Cytokine levels were determined by ELISA, and corresponding mRNA expression was analyzed via RT-PCR. Kidney injury severity was evaluated histologically by pathologists. Protein levels of neutrophil gelatinase-associated lipocalin and high mobility group box 1 were examined by Western blot.
VISTA expression was significantly elevated on circulating neutrophils and monocytes following injury (all p < 0.05). Histopathological assessment revealed aggravated kidney injury in the AKI model (p = 0.0056), which was further exacerbated in VISTA-deficient mice (p = 0.0357). Consistent with this, serum creatinine (p = 0.014) and blood urea nitrogen (p = 0.005) levels were markedly higher in VISTA-deficient mice compared to controls. Pro-inflammatory cytokines IL-6 (p = 0.0335) and TNF-α (p = 0.0283) were increased in AKI mice and further elevated in VISTA-deficient mice (p = 0.0014 and 0.0001, respectively), whereas anti-inflammatory IL-10 showed a converse trend (p = 0.0056 and 0.0019, respectively). RT-PCR confirmed corresponding changes in cytokine mRNA expression. Western blot analysis indicated decreased neutrophil gelatinase-associated lipocalin (p < 0.0001) and increased high mobility group box 1 protein (p = 0.0009) levels in VISTA-deficient mice.
Collectively, our results demonstrate that VISTA‑deficient mice develop more severe early‑phase hemorrhage/sepsis‑induced AKI. Altered NGAL and HMGB1 protein expression occur in parallel with VISTA‑associated renal protection; further functional validation is required to establish causal mechanistic relationships and to evaluate the translational potential of VISTA‑targeted approaches.

PMID:
42829648
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

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