ArticleNature communications2023
MANF stimulates autophagy and restores mitochondrial homeostasis to treat autosomal dominant tubulointerstitial kidney disease in mice.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- The role of mesencephalic astrocyte-derived neurotrophic factor in digestive diseases.Annals of medicine · 2026Review
- Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis.Bioactive materials · 2026Article
- Calorie Restriction Leads to Degradation of Mutant Uromodulin and Ameliorates Inflammation and Fibrosis in UMOD -Related Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.Cell biology and toxicology · 2026Article
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Autosomal Dominant Tubulointerstitial Kidney Disease-UMOD: Case Report and Disease Update.Diagnostics (Basel, Switzerland) · 2026Article
- Uromodulin p.His36Tyr promotes macrophage pyroptosis via App-Cd74 signaling to drive renal inflammation in ADTKD.Nature communications · 2026Article
- Emerging Mechanistic Roles of STING Signaling in Kidney Diseases.The American journal of pathology · 2026Review
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Plasma Metabolites Associated with CKD Stage in Autosomal Dominant Tubulointerstitial Kidney Disease.Kidney360 · 2026Article
- cGAS-STING and autophagy: crosstalk, molecular mechanisms, and targeted therapy.Archives of toxicology · 2026Review
- The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment Modulation.International journal of biological sciences · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Upregulated astrocytic HDAC7 induces depression-like disorders via deacetylating PINK1 and inhibiting mitophagy.Journal of neuroinflammation · 2025Article
- Identification and validation of the pivotal role of MANF gene in pancreatic β-cell aging using bioinformatics.Biochemistry and biophysics reports · 2025Article
- Autosomal dominant tubulointerstitial kidney disease-UMOD: a short review.Orphanet journal of rare diseases · 2025Review
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- N6-methyladenosine-mediated upregulation of MANF promotes ER stress resistance in renal cell carcinoma.Cell death & disease · 2025Article
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19 authors at 6 institutions in 3 countries.
Funding
Abstract
Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), a leading hereditary kidney disease. There are no targeted therapies. In our generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are impaired, leading to cGAS-STING activation and tubular injury. Moreover, we demonstrate that inducible tubular overexpression of mesencephalic astrocyte-derived neurotrophic factor (MANF), a secreted endoplasmic reticulum protein, after the onset of disease stimulates autophagy/mitophagy, clears mutant UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, thus protecting kidney function in our ADTKD mouse model. Conversely, genetic ablation of MANF in the mutant thick ascending limb tubular cells worsens autophagy suppression and kidney fibrosis. Together, we have discovered MANF as a biotherapeutic protein and elucidated previously unknown mechanisms of MANF in the regulation of organelle homeostasis, which may have broad therapeutic applications to treat various proteinopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.