ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- circCACNA1D drives pulmonary fibrosis by regulating pyruvate kinase M2 dimer‑tetramer switching.International journal of molecular medicine · 2026Article
- Insulin-like growth factor-binding protein 7 is a soluble cell adhesion molecule.Science advances · 2026Article
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Renal Tubular Epithelial CRLF1 Interacts With ITGB1 to Accelerate Fibrosis During the Transition From AKI to CKD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ANGPTL4 Exacerbates Renal Injury in Diabetic Kidney Disease by Impairing Podocyte Lipophagy via Compromised Lysosomal Degradative Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fatty Kidney: The Interplay of Lipids and Diabetic Kidney Disease.Biomedicines · 2026Review
- The biology of PKM2 in the metabolism and senescence in diabetic kidney disease.Journal of diabetes investigation · 2026Review
- Trichostatin A Influences Dendritic Cells' Functions by Regulating Glucose and Lipid Metabolism via PKM2.Molecules (Basel, Switzerland) · 2026Article
- GIPC2 regulation of the PKM2/SREBP1 signaling axis controls adipogenic differentiation of mesenchymal stem cells.Cell death & disease · 2026Article
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Targeting tubular epithelial cell metabolism to halt renal fibrosis: current evidence and future directions.Frontiers in cell and developmental biology · 2026Review
- Lipid metabolism drives podocyte injury in diabetic kidney disease.Frontiers in immunology · 2026Review
- Pathologic Signaling and Disease Implications of Insulin-like Growth Factor Binding Proteins in Cancer, Cardiovascular Disease, and Fibrosis.International journal of molecular sciences · 2025Review
- IGFBP7: A potential target for tubular lipogenesis in CKD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal fibrosis serves as a critical pathological mechanism driving the progression of chronic kidney disease (CKD). However, the pathogenesis and therapeutic targets involved in this process remain unclear. Interestingly, we currently found that IGFBP7 is highly expressed in tubular epithelial cells (TECs) from the fibrotic kidneys of human patients and animal models. However, their functional roles in abnormal kidney repair and renal fibrosis remain unclear. Here, we report that IGFBP7 knockout (KO) or TEC conditional KO (cKO) attenuated renal fibrosis in multiple mouse models, whereas IGFBP7 knock-in or restoration in IGFBP7-KO mice enhanced renal fibrosis. These in vivo findings were verified using cultured TECs and organoids generated from IGFBP7-cKO mice. Mechanistically, we found that IGFBP7 bound to pyruvate kinase M2 (PKM2) to promote the acetylation of PKM2 at the K433 site, thereby enhancing PKM2 dimerization and nuclear translocation, and subsequently accelerating lipid production and renal fibrosis via SREBP1-dependent mechanisms. Notably, through drug screening, we identified salmeterol (an asthma medication) as an IGFBP7 antagonist that effectively reduced fibrosis. Our findings reveal the IGFBP7/PKM2/SREBP1 axis as a central regulator of lipogenic fibrosis, offering genetic and pharmacological inhibition of IGFBP7 as promising therapeutic strategies for CKD.
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