Academic Journal
The telomerase reverse transcriptase-derived peptide GN11 alleviates glycolysis and cellular senescence in the fibrotic kidney by inhibiting the TGF-β1/Smad3/lncRNA Oip5-os1/miR-30c-5p/Rock2 axis.
| Τίτλος: | The telomerase reverse transcriptase-derived peptide GN11 alleviates glycolysis and cellular senescence in the fibrotic kidney by inhibiting the TGF-β1/Smad3/lncRNA Oip5-os1/miR-30c-5p/Rock2 axis. |
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| Συγγραφείς: | Yang R; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Zhang J; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Feng X; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Huang R; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Wang W; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Chen W; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Liu Y; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Chen T; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Bai J; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Lei H; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Zhang J; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Rao S; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China., Zhang B; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, Lanzhou University, Lanzhou 730000, China. Electronic address: zhangbz@lzu.edu.cn. |
| Πηγή: | Biochemical pharmacology [Biochem Pharmacol] 2026 Jul; Vol. 249, pp. 117902. Date of Electronic Publication: 2026 Mar 14. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| Ιατρικοί όροι (MeSH): | MicroRNAs*/metabolism , MicroRNAs*/antagonists & inhibitors , MicroRNAs*/genetics , RNA, Long Noncoding*/metabolism , RNA, Long Noncoding*/antagonists & inhibitors , RNA, Long Noncoding*/genetics , Cellular Senescence*/drug effects , Cellular Senescence*/physiology , rho-Associated Kinases*/metabolism , rho-Associated Kinases*/antagonists & inhibitors , rho-Associated Kinases*/genetics , Telomerase*/chemistry , Telomerase*/metabolism , Telomerase*/pharmacology , Transforming Growth Factor beta1*/metabolism , Transforming Growth Factor beta1*/antagonists & inhibitors , Glycolysis*/drug effects , Glycolysis*/physiology , Kidney*/drug effects , Kidney*/pathology , Kidney*/metabolism , Peptide Fragments*/pharmacology, Signal Transduction/drug effects ; Animals ; Humans ; Fibrosis ; Mice ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Renal fibrosis represents the ultimate pathological manifestation of chronic kidney disease (CKD). To date, no clinically approved drugs that specifically target renal fibrosis are available. In this study, we discovered that GV1001(GV), a peptide fragment derived from human telomerase reverse transcriptase (hTERT), can inhibit the unilateral ureteral obstruction (UUO)-induced renal fibrosis. Through systematic fragment optimization, we identified GN11, an analog of GV with superior activity. The phenotypic analysis revealed that both GV and its optimized analog GN11 effectively attenuated glycolysis, cellular senescence and apoptotic phenotypes associated with renal fibrosis. Mechanistic investigations indicated that GN11 suppresses TGF-β1/Smad3 signaling while upregulates the expression of miR-30c-5p, leading to the downregulation of its target gene Rock2. Furthermore, GN11 reduces the expression of the lncRNA Oip5-os1, thereby diminishing its antagonistic effect on miR-30c-5p, which in turn amplifies the inhibitory effect on Rock2 expression. These findings suggest that GN11 has promising potential as a candidate molecule for the treatment of renal fibrosis and other types of organ fibrosis. Moreover, our research provides valuable insights and a scientific foundation for the development of novel therapeutic agents against renal fibrosis. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cellular senescence; GN11; Glycolysis; Peptide; Renal fibrosis; Rock2; lncRNA Oip5-os1; miR-30c-5p |
| Substance Nomenclature: | 0 (MicroRNAs) 0 (RNA, Long Noncoding) EC 2.7.11.1 (rho-Associated Kinases) EC 2.7.7.49 (Telomerase) 0 (Transforming Growth Factor beta1) 0 (MIRN30a microRNA, mouse) 0 (Peptide Fragments) |
| Entry Date(s): | Date Created: 20260316 Date Completed: 20260711 Latest Revision: 20260711 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.bcp.2026.117902 |
| PMID: | 41839244 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2026.117902 |