HMGN5 promotes renal tubular inflammation and pyroptosis-associated signaling in chronic kidney disease via the IFNAR2 axis
- 1Medical Administration Office, Shijiazhuang People's Hospital, Shijiazhuang, Hebei 050011, P.R. China
- 2Department of Nephrology, Shijiazhuang People's Hospital, Shijiazhuang, Hebei 050011, P.R. China
Abstract
Chronic kidney disease (CKD) is a condition that is characterized by persistent tubular injury, inflammation and progressive fibrosis, ultimately leading to an irreversible loss of renal function. Pyroptosis, a notably pro-inflammatory mode of programmed cell death, contributes to tubular epithelial injury and amplifies renal inflammwation. The present study investigated the role of high mobility group nucleosome-binding protein 5 (HMGN5) in CKD and its regulatory relationship with interferon (IFN) receptor 2 (IFNAR2) signaling. The present study found that HMGN5 expression was significantly upregulated in renal tissues obtained from patients with CKD and CKD-model mice; this upregulation was accompanied by enhanced renal injury, fibrosis and inflammatory cytokine production. In vitro, HMGN5 overexpression in HK-2 cells: i) Promoted the expression of IFNAR2, phosphorylated-interferon regulatory factor (IRF)3/IRF7 and absent in melanoma 2; ii) enhanced the cleavage of caspase-1 and gasdermin D; iii) increased IL-1β, IL-8 and IFN-β secretion; and iv) promoted lactate dehydrogenase release. These findings suggested the activation of pyroptosis-associated cellular responses. Conversely, silencing HMGN5 or blocking IFNAR2 signaling markedly attenuated these effects. In vivo, pharmacological blockade of IFNAR2 ameliorated renal tissue damage, reduced fibrosis, restored renal function, decreased systemic cytokine levels and suppressed pyroptosis-associated signaling in CKD-model mice. Collectively, the findings of the present study identified HMGN5 as a novel regulator of IFNAR2-related pyroptosis-associated signaling in renal tubular epithelial cells and suggested that the HMGN5-IFNAR2 axis represents a pathophysiological pathway of interest in CKD that warrants further investigation.
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BibTeX
@article{rong2026hmgn5,
title = {{HMGN5 promotes renal tubular inflammation and pyroptosis-associated signaling in chronic kidney disease via the IFNAR2 axis}},
author = {Xue Rong and Jing Xu and Jienan Zhang and Qi Zhang and Jiangli Wang and Guoxin Zhang and Limin Nie},
journal = {International Journal of Molecular Medicine},
year = {2026},
month = oct,
doi = {10.3892/ijmm.2026.6022},
url = {https://doi.org/10.3892/ijmm.2026.6022},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - HMGN5 promotes renal tubular inflammation and pyroptosis-associated signaling in chronic kidney disease via the IFNAR2 axis
AU - Xue Rong
AU - Jing Xu
AU - Jienan Zhang
AU - Qi Zhang
AU - Jiangli Wang
AU - Guoxin Zhang
AU - Limin Nie
PY - 2026
DA - 2026/10/22
JO - International Journal of Molecular Medicine
DO - 10.3892/ijmm.2026.6022
UR - https://doi.org/10.3892/ijmm.2026.6022
AB - Chronic kidney disease (CKD) is a condition that is characterized by persistent tubular injury, inflammation and progressive fibrosis, ultimately leading to an irreversible loss of renal function. Pyroptosis, a notably pro-inflammatory mode of programmed cell death, contributes to tubular epithelial injury and amplifies renal inflammwation. The present study investigated the role of high mobility group nucleosome-binding protein 5 (HMGN5) in CKD and its regulatory relationship with interferon (IFN) receptor 2 (IFNAR2) signaling. The present study found that HMGN5 expression was significantly upregulated in renal tissues obtained from patients with CKD and CKD-model mice; this upregulation was accompanied by enhanced renal injury, fibrosis and inflammatory cytokine production. In vitro, HMGN5 overexpression in HK-2 cells: i) Promoted the expression of IFNAR2, phosphorylated-interferon regulatory factor (IRF)3/IRF7 and absent in melanoma 2; ii) enhanced the cleavage of caspase-1 and gasdermin D; iii) increased IL-1β, IL-8 and IFN-β secretion; and iv) promoted lactate dehydrogenase release. These findings suggested the activation of pyroptosis-associated cellular responses. Conversely, silencing HMGN5 or blocking IFNAR2 signaling markedly attenuated these effects. In vivo, pharmacological blockade of IFNAR2 ameliorated renal tissue damage, reduced fibrosis, restored renal function, decreased systemic cytokine levels and suppressed pyroptosis-associated signaling in CKD-model mice. Collectively, the findings of the present study identified HMGN5 as a novel regulator of IFNAR2-related pyroptosis-associated signaling in renal tubular epithelial cells and suggested that the HMGN5-IFNAR2 axis represents a pathophysiological pathway of interest in CKD that warrants further investigation.
SN - 1107-3756
SN - 1791-244X
ER -