ArticleLupus science & medicine2024
HNF-1β alleviates podocyte injury in lupus nephritis by maintaining endoplasmic reticulum homeostasis.
Article in Lupus science & medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An Insight into Molecular Mechanisms and Therapeutic Approaches.Molecular neurobiology · 2026Review
- Dual-mechanistic regulation of podocyte pyroptosis in lupus nephritis by the AP-1 complex: transcriptional activation of NLRP3 and lactate-mediated ubiquitination inhibition.Cell communication and signaling : CCS · 2026Article
- The Pathogenic Role of T Cell Metabolism and its Effect on Immune Senescence in Autoimmune Diseases and Infection.Clinical reviews in allergy & immunology · 2025Review
- Effects of environmentally-induced anxiety on autoimmunity in the MRL/lpr mouse.Lupus science & medicine · 2025Article
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Authors and funding
13 authors.
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Abstract
objectiveThe current study aims to elucidate the critical function of hepatocyte nuclear factor 1-beta (HNF1-β) in lupus nephritis (LN) by investigating its modulation of the Derlin-1/valosin-containing protein (VCP)/VCP-interacting membrane selenoprotein (VIMP) complex, endoplasmic reticulum (ER) stress and podocyte apoptosis.
methodsIn vitro and in vivo models of LN were established using glomerular podocytes treated with LN serum and MRL/lpr mice, respectively. The expression levels of HNF1-β were analysed in kidney tissues from patients with LN and MRL/lpr mice. To assess the effects of HNF1-β inhibition, an adeno-associated virus vector carrying HNF1-β short hairpin was administered to MRL/lpr mice. In vitro, glomerular podocytes were transfected with HNF1-β small interfering RNA (siRNA) or HNF1-β overexpression plasmids to explore their regulatory effects on the Derlin-1/VCP/VIMP complex and podocyte apoptosis. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were performed to investigate the transcriptional activation of Derlin-1 and VCP promoters by HNF1-β.
resultsA significant decrease in HNF1-β levels was observed in kidney tissues from patients with LN while MRL/lpr mice exhibited an initial compensatory increase followed by a subsequent decrease in renal HNF1-β expression. Overexpression of HNF1-β transcriptionally upregulated Derlin-1 and VCP mitigating LN serum-induced ER stress and podocyte apoptosis. In contrast, HNF1-β inhibition exacerbated renal dysfunction and structural damage in MRL/lpr mice. Interestingly, HNF1-β inhibition transcriptionally repressed ERP44, leading to calcium ions (Ca²
conclusionThis study provides novel insights into the regulatory mechanisms of HNF1-β in LN emphasising its impact on the Derlin-1/VCP/VIMP complex, ER stress and podocyte apoptosis. These findings have the potential to inform the development of new diagnostic tools and therapeutic strategies for LN.
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