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The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.

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Τίτλος: The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.
Συγγραφείς: Shang Y; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Wang Y; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Luo Q; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., He R; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Wang S; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Wang B; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Lin W; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., Zhou Y; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., He Q; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China., He Q; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China. qianghe1973@126.com.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China. qianghe1973@126.com., Jin J; Department of Nephrology, The First Affiliated Hospital of Zhejiang, Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, Zhejiang, China. lang_018@163.com.; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease; Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology; Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China. lang_018@163.com.
Πηγή: Seminars in immunopathology [Semin Immunopathol] 2026 Aug 24; Vol. 48 (1). Date of Electronic Publication: 2026 Aug 24.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: Germany NLM ID: 101308769 Publication Model: Electronic Cited Medium: Internet ISSN: 1863-2300 (Electronic) Linking ISSN: 18632297 NLM ISO Abbreviation: Semin Immunopathol Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin : Springer
Ιατρικοί όροι (MeSH): Macrophages*/metabolism , Macrophages*/immunology , Kidney Tubules*/metabolism , Kidney Tubules*/pathology , Kidney Diseases*/metabolism , Kidney Diseases*/etiology , Kidney Diseases*/pathology , Cell Communication* , Cellular Reprogramming*, Humans ; Metabolic Reprogramming ; Fibrosis ; Animals ; Signal Transduction
Περίληψη: Kidney fibrosis is the histopathological endpoint of chronic kidney disease, yet antifibrotic trials targeting individual molecular nodes have repeatedly failed to translate into patient benefit. The pattern suggests that renal fibrosis is sustained by a recurrent circuit rather than a linear cascade. Here we propose a tubular-macrophage lactate-lactylation circuit that integrates tubular and macrophage evidence into a single cellular axis. Injured tubular cells reprogramme glycolytically and generate a sustained lactate-rich niche. On both sides of the tubulointerstitial interface, lactate is converted into histone and non-histone lactyl-lysine (Kla) marks that lock in profibrotic transcription, derange mitochondrial function and dampen innate immune surveillance. Macrophage outputs, profibrotic macrophage programmes, innate-immune memory, paracrine activation of fibroblasts/pericytes and, in selected contexts, macrophage-to-myofibroblast transition, feed back on tubular cells and the stromal compartment through bidirectional vesicular and cytokine signalling, generating the recurrent topology that distinguishes a circuit from a linear pathway. The supporting evidence is uneven across compartments; we stratify each key claim by tier of evidence and map the circuit onto current biomarker and therapeutic strategies. The framework clarifies why single-node interventions have not succeeded, and points to combinations that engage substrate supply, lactylation machinery, transcriptional output and intercellular feedback in parallel.
(© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Competing Interests: Declarations. Competing interest: The authors declare no competing of interest.
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Grant Information: 2025ZY01110 Central Government Guides Local Science and Technology Development Fund Projects; ZYYCXTD-D-202402 National Traditional Chinese Medicine Multidisciplinary Innovation Team; GZY-ZJ-KJ-24014 Key Project of the Scientific Research Foundation of Chinese Medicine
Contributed Indexing: Keywords: Intercellular signalling; Kidney fibrosis; Lactylation; Metabolic reprogramming; Tubular–macrophage crosstalk
Entry Date(s): Date Created: 20260824 Date Completed: 20260824 Latest Revision: 20260824
Update Code: 20260825
DOI: 10.1007/s00281-026-01083-y
PMID: 42635816
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1863-2300
DOI:10.1007/s00281-026-01083-y