Peptides最新文献

{"title":"Ghrelin attenuates skeletal-muscle atrophy by regulating muscle protein degradation and lung inflammation in aged male mice with lipopolysaccharide-induced lung injury","authors":"Moeka Honda ,&nbsp;Hironobu Tsubouchi ,&nbsp;Rika Inomata ,&nbsp;Shigehisa Yanagi ,&nbsp;Katsuya Sakai ,&nbsp;Kazutaka Shiomi ,&nbsp;Masamitsu Nakazato ,&nbsp;Taiga Miyazaki","doi":"10.1016/j.peptides.2026.171478","DOIUrl":"10.1016/j.peptides.2026.171478","url":null,"abstract":"<div><div>Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by reduced muscle mass and strength, leading to adverse outcomes such as frailty and increased mortality. Pneumonia can accelerate the progression of sarcopenia, particularly in older adults, by promoting systemic inflammation, reducing physical activity, and impairing respiratory and swallowing muscle function. No effective therapeutic interventions for sarcopenia have been established. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced primarily in the stomach and is known to stimulate appetite, suppress inflammation, and prevent muscle catabolism. Here, we showed that intraperitoneal ghrelin given every 12 h attenuated skeletal-muscle atrophy in aged mice with lipopolysaccharide (LPS)-induced lung injury. Ghrelin treatment preserved muscle weight and mass, suppressed the FoxO1-dependent expression of muscle-specific E3 ubiquitin ligases, muscle RING-finger protein-1, and F-Box protein 32 in the gastrocnemius muscle, and improved the muscle contractile force and voluntary wheel-running activity. In parallel, ghrelin treatment attenuated histological lung injury and was associated with lower levels of inflammatory cytokines in bronchoalveolar lavage fluid. In vitro, ghrelin treatment of LPS-stimulated C2C12 myotubes suppressed reactive oxygen species accumulation and increased the expression of redox-regulating genes including peroxisome proliferator-activated receptor gamma coactivator 1-α and superoxide dismutase 2. Ghrelin also downregulated the LPS-induced expression of muscle-specific ubiquitin ligases in C2C12 cells. These findings suggest that ghrelin has a protective role against inflammation-associated skeletal-muscle atrophy and may have potential as a therapeutic agent for respiratory sarcopenia in the elderly.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171478"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes","authors":"Clifford J. Bailey ,&nbsp;Peter R. Flatt ,&nbsp;J. Michael Conlon","doi":"10.1016/j.peptides.2026.171480","DOIUrl":"10.1016/j.peptides.2026.171480","url":null,"abstract":"<div><div>The first therapeutically useful amylin receptor (AMYR) agonist, pramlintide was based upon the structure of non-aggregating rat amylin and found limited application as an adjunct to insulin therapy. It acts centrally to induce satiety, promote weight loss, suppress prandial glucagon release and reduce prandial hyperglycaemia. Recent understanding of the heterodimeric structure of amylin-calcitonin receptor complexes and of amylin structure-function properties has assisted the design of a second generation of non-aggregating, long-acting amylin analogues. These are now advancing in clinical development and promise to provide an effective additional resource for the management of obesity and type 2 diabetes. Amongst these agents is the dual AMYR/ calcitonin-receptor (CTR) agonist, cagrilintide that has also been co-formulated into a once weekly subcutaneous injection with the long-acting glucagon-like peptide-1receptor (GLP-1R) agonist, semaglutide (CagriSema). In clinical trials, CagriSema has achieved greater effects than either component alone. A unimolecular AMYR/CTR/GLP-1R multi-agonist peptide, amycretin has been developed for weekly injection and as a once-daily tablet. Several recently developed long-acting amylin analogues have shown strong efficacy as monotherapy in clinical trials: these include eloralintide, petrelintide, Met-233 and AZD6234. Other analogues with marked efficacy in preclinical studies, including non-peptide AMYR agonists are under development. Gastrointestinal side effects, especially nausea, similar to those reported for GLP-1R agonists are commonplace during initiation and up-titration of amylin analogues but mostly resolve during continued use. Evidence is emerging that long-acting AMYR agonists may show potential therapeutic benefits in treatment of patients with fatty liver disease, diabetes-associated kidney complications and resistant hypertension.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171480"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF9 drives mitochondrial biogenesis in glioblastoma by activating the CREB-PGC-1α axis","authors":"Kun Xue ,&nbsp;Junmei Yang ,&nbsp;Jia Hu ,&nbsp;Lingwei Kong ,&nbsp;Xinguo Cui ,&nbsp;Yang Kong","doi":"10.1016/j.peptides.2025.171463","DOIUrl":"10.1016/j.peptides.2025.171463","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial biogenesis is upregulated in glioblastoma to support tumor growth, invasion, and chemoresistance by meeting the heightened metabolic demands of cancer cells. Fibroblast growth factor 9 (FGF9) is a potent oncogenic driver in various cancers, promoting proliferation, survival, and angiogenesis. However, its role in regulating mitochondrial metabolism in glioblastoma remains unclear.</div></div><div><h3>Methods</h3><div>The activation of FGF9/fibroblast growth factor receptor 2 (FGFR2) signaling and expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) were examined in clinical glioblastoma samples and cell lines using real-time PCR, immunohistochemistry, and western blotting. Mitochondrial biogenesis and function in FGF9-treated U-87 cells were evaluated by measuring relative mtDNA/nDNA ratio, mitochondrial mass (MitoTracker), complex activity, membrane potential, and ATP production. The role of cAMP response element-binding protein (CREB) signaling was investigated using the specific inhibitor H89.</div></div><div><h3>Results</h3><div>We found activated FGF9/FGFR2 signaling in glioblastoma patients, with elevated serum FGF9 and tumor FGFR2. PGC-1α was upregulated in samples and cell lines. FGF9 boosted mitochondrial biogenesis and function in U-87 cells, increasing mtDNA, mass, complex activity, membrane potential, and ATP production. Mechanistically, FGF9 promoted the expression of PGC-1α and mitochondrial transcription factor A (TFAM) via activation of CREB signaling. Inhibition of CREB phosphorylation by H89 abolished FGF9-induced upregulation of PGC-1α/TFAM, mtDNA replication, and ATP production.</div></div><div><h3>Conclusion</h3><div>These findings reveal that FGF9 enhances mitochondrial biogenesis in glioblastoma through the CREB-PGC-1α-TFAM axis, uncovering a novel metabolic mechanism underlying its pro-tumorigenic effects.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171463"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menstrual cycle phase and hormonal contraceptive use influence circulating proforms of atrial natriuretic peptide, adrenomedullin, and the vasopressin proxy copeptin in healthy women","authors":"Anne Sophie Broholt Jensen ,&nbsp;Janne Gasseholm Bentzen ,&nbsp;Jens P. Goetze ,&nbsp;Mette Hansen ,&nbsp;Tine Vrist Dam ,&nbsp;Sara A. Christensen ,&nbsp;Trine Pagh Ludvigsen ,&nbsp;Michael Nyberg ,&nbsp;Dijana Terzic","doi":"10.1016/j.peptides.2026.171465","DOIUrl":"10.1016/j.peptides.2026.171465","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease is the main cause of mortality among women. However, the menstrual cycle and hormonal contraception are often overlooked in research. This study investigates whether concentrations of common cardiovascular biomarkers (natriuretic peptides, adrenomedullin, and copeptin) change during a menstrual cycle and with hormonal contraception use.</div></div><div><h3>Methods</h3><div>Concentrations of cardiovascular biomarkers in 2 prospective cohorts were measured. In <em>The Menstrual Cycle Study</em>, blood samples were collected throughout a menstrual cycle, and in <em>The Contraception Study</em>, blood samples were collected from women using different contraceptive methods.</div></div><div><h3>Results</h3><div>Blood samples from 19 women (<em>The Menstrual Cycle study</em>) and 638 women (<em>The Contraception Study</em>) were analyzed. Concentrations of mid-regional (MR)-pro-atrial natriuretic peptide (proANP) are highest during the early follicular phase (Delta %: median: 111.5 %, IQR: 100.6–115.9 %) and lowest during the mid-luteal phase (median: 88.0 %, IQR: 80.4–103.2 %) (<em>P</em> = .02). When compared to women with natural cycles, median concentrations of MR-proANP were reduced by 19.3 % in those using combined oral contraceptives (COC)/vaginal contraceptive ring and by 18.2 % in progestin-users. Additionally, copeptin concentrations were reduced by 11.9 % in COC/vaginal contraceptive ring-users, while MR-proadrenomedullin (proADM) concentrations were reduced by 15.4 % in COC/vaginal contraceptive ring-users and 11.5 % in progestin-users compared to non-users.</div></div><div><h3>Conclusions</h3><div>MR-proANP concentrations vary across the menstrual cycle with the highest concentrations during the early follicular phase. Furthermore, concentrations of MR-proANP, copeptin, and MR-proADM are affected by hormonal contraception. Our findings underscore the necessity to consider menstrual cycle phases and use of hormonal contraception in clinical assessment of premenopausal women when using cardiovascular biomarkers.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171465"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the angiotensin-(1−7) on the vascular effects of the endothelin-1 in normotensive and hypertensive rats","authors":"Jaqueline Moura da Costa ,&nbsp;Amanda de Sá Martins de Bessa ,&nbsp;Lara Marques Naves ,&nbsp;Monique Machado Louredo Teles ,&nbsp;Gustavo Rodrigues Pedrino ,&nbsp;Elizabeth Pereira Mendes ,&nbsp;Carlos Henrique de Castro","doi":"10.1016/j.peptides.2025.171455","DOIUrl":"10.1016/j.peptides.2025.171455","url":null,"abstract":"<div><div>Angiotensin-(1−7) [Ang-(1−7)] exerts cardioprotective effects through Mas receptor activation. Endothelin-1 (ET-1) is implicated in cardiovascular pathologies. Previous studies indicate a cross-talk between angiotensin and endothelin pathways; however, it remains unclear whether Ang-(1−7) differentially modulates vascular responses to ET-1 in normotensive and hypertensive conditions. This study investigated the influence of Ang-(1−7) on ET-1–induced pressor and vascular responses in normotensive and hypertensive rats (SHR). Blood pressure was recorded in conscious animals. Vascular reactivity was assessed in isolated aortic rings, and coronary effects were assessed in isolated hearts using the Langendorff technique. ET-1 increased blood pressure and reduced heart rate only in Wistar rats, effects abolished by Ang-(1−7). In normotensive rats, Ang-(1−7) potentiated ET-1–induced vasoconstriction in endothelium-intact aortas independently of Mas receptors, but had no effect in the aorta without endothelium. In hypertensive rats, Ang-(1−7) attenuated ET-1 responses in endothelium-intact aorta via Mas receptor, whereas in endothelium-denuded vessels it potentiated the vasoconstriction. In isolated hearts, ET-1 produced a biphasic response in normotensive rats (vasodilation followed by vasoconstriction) but only vasoconstriction in hypertensive rats. Ang-(1−7) potentiated vasoconstriction in normotensive but attenuated it in hypertensive hearts, which was abolished by Mas receptor blockade. These findings demonstrate that Ang-(1−7) differentially modulates ET-1 actions in normotensive and hypertensive conditions, reinforcing RAS–endothelin cross-talk. Its counter-regulatory effect in hypertension highlights Ang-(1−7) as a promising therapeutic target in cardiovascular disease.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171455"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct and complementary metabolic effects of GLP-1 and glucagon receptor agonism in diet-induced obese mice","authors":"Marie Winther-Sørensen ,&nbsp;Christine Rasmussen ,&nbsp;Samuel A.J. Trammell ,&nbsp;Caroline Hansen ,&nbsp;Mogens Vyberg ,&nbsp;Reza Serizawa ,&nbsp;Erik A. Richter ,&nbsp;Trisha J. Grevengoed ,&nbsp;Lise Lotte Gluud ,&nbsp;Rune E. Kuhre ,&nbsp;Nicolai J. Wewer Albrechtsen","doi":"10.1016/j.peptides.2025.171462","DOIUrl":"10.1016/j.peptides.2025.171462","url":null,"abstract":"<div><div>Glucagon-like peptide-1 (GLP-1) and glucagon receptor co-agonism is an emerging therapeutic strategy for obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). To examine their distinct and combined metabolic actions in a model reflecting chronic disease, we used diet-induced obese mice that had been maintained on high-fat diet from early adulthood, allowing obesity and hepatic steatosis to develop gradually and remain stable before initiating treatment. Mice received a long-acting GLP-1 receptor agonist (NNC2220), a long-acting glucagon receptor agonist (NNC9204–0043), or both for 28 days, and a calorie-restricted weight-matched group was included to separate drug-specific from weight-dependent effects. Monotherapy with either agonist produced similar weight loss of approximately 24 %, whereas combined treatment resulted in a substantially greater reduction of 37 %. GLP-1 agonism decreased food intake, whereas glucagon agonism did not; however, glucagon agonism produced a larger reduction in hepatic triglycerides than GLP-1 agonism or weight matching, indicating hepatic effects not explained solely by weight loss. Chronic glucagon receptor activation also increased hepatic glycogen content, both alone and in combination therapy, without corresponding changes in glycogen synthase or phosphorylase activities, suggesting regulation upstream of these enzymatic pathways. These data show that combined GLP-1 and glucagon receptor agonism enhances weight loss and reduces hepatic lipid content beyond GLP-1 agonism alone. Because energy expenditure and dynamic glucose tolerance were not directly assessed, mechanistic interpretation is limited. Glucagon receptor signaling may be a key contributor to hepatic lipid metabolism and support its therapeutic potential—alone or combined with GLP-1 agonism—for improving liver health in MASLD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171462"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral salmon acylated ghrelin increases food intake in common carp (Cyprinus carpio) via ghrelin receptors, likely through sensory nerves rather than systemic absorption","authors":"Minoru Kihara ,&nbsp;Teppei Yamagiwa ,&nbsp;Hidekazu Katayama ,&nbsp;Hiroyuki Kaiya","doi":"10.1016/j.peptides.2026.171464","DOIUrl":"10.1016/j.peptides.2026.171464","url":null,"abstract":"<div><div>This study clarified the local mechanism of action and assessed the aquaculture potential of orally administered salmon acylated ghrelin (sAG) on feed intake in common carp (<em>Cyprinus carpio</em>). Experimental diets containing sAG (ranging from 0.001 to 13.04 µg/g) were prepared and fed to carp at 2.0 % of body weight (BW) in single-shot trials. Fish receiving diets of 0.64 µg/g (1.3 µg/100 g BW) or higher exhibited a significant, dose-dependent increase in additional feed intake, plateauing at 1.20 µg/g (2.4 µg/100 g BW). Despite this behavioral effect, plasma ghrelin levels remained unchanged, as measured by both N-terminal and salmon-specific C-terminal radioimmunoassays, confirming that sAG was not systemically absorbed. The orexigenic effect was abolished by pretreatment with the ghrelin receptor antagonist [<span>D</span>-Lys3]-GHRP-6 or with capsaicin, demonstrating local sAG action via growth hormone secretagogue receptor signaling and peripheral sensory neurons (likely vagal afferents). These findings provide the first evidence that fish ghrelin exerts biological activity via a non-circulatory neuroendocrine pathway. This advances our understanding of the vertebrate gut–brain axis and highlights the potential of harnessing locally acting peptides for physiological modulation in aquatic species.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171464"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymosin beta 4: An emerging therapeutic candidate for kidney diseases","authors":"Huajie Di ,&nbsp;Jiaxin Huang ,&nbsp;Dexin Zhang,&nbsp;Fei Ni,&nbsp;Rui Zheng,&nbsp;Hongquan Geng","doi":"10.1016/j.peptides.2026.171467","DOIUrl":"10.1016/j.peptides.2026.171467","url":null,"abstract":"<div><div>Over the past decades, the escalating global burden of kidney disease has underscored an urgent need for innovative therapeutic strategies. Thymosin β4 (Tβ4), a highly conserved 43-amino-acid peptide encoded by the X-linked <em>TMSB4x</em> gene, is the predominant β-thymosin in mammalian cells and a multifunctional regulator of cellular homeostasis. Once considered mainly an actin-sequestering molecule, Tβ4 and its N-terminal metabolite N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) now emerge as dynamic mediators of renal injury and repair. In this review, we synthesize current evidence on the Tβ4–Ac-SDKP axis. We map intra- and extracellular mechanisms and relevant signaling pathways, delineate cell-type and spatial expression across glomerular and tubular compartments, and critically evaluate its renoprotective efficacy—including cytoprotection, anti-inflammatory and antifibrotic actions—across models of acute and chronic kidney injury. To reconcile disparate findings, we propose conceptual frameworks that consider bidirectional effects on fibrosis and model-dependent mechanisms. Finally, translational opportunities are appraised with attention to pharmacokinetics, peptide stability and delivery strategies. Key challenges moving forward include validating efficacy in additional clinically relevant models, overcoming peptide instability and completing comprehensive safety assessments.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171467"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-peptide bradykinin B2 receptor ligands possessing the substituted quinolinyl moiety: Pharmacological properties and prospective clinical uses","authors":"Ahmed Sahli ,&nbsp;René C.-Gaudreault ,&nbsp;François Marceau","doi":"10.1016/j.peptides.2026.171466","DOIUrl":"10.1016/j.peptides.2026.171466","url":null,"abstract":"<div><div>Bradykinin is a nonapeptide derived from the cleavage of circulating kininogens by plasma or tissue kallikreins and is endowed with powerful pharmacologic actions, such as the production of protein-rich exudates and vasodilation. The widely expressed B2 receptor for bradykinin (a G protein-coupled receptor) has been the focus of intense drug development efforts for more than 4 decades, with marked differences in affinities and competitiveness for synthetic antagonists across mammalian species. Many non-peptide ligands of the human B2 receptor have been developed by various industrial organizations. A recurring substituted 8-[(2,6-dichlorophenyl)methoxy]-2-methylquinolinyl (\"quinolyl\") moiety, or variants thereof, was explored by several pharmaceutical organizations. FR173657, fasitibant, anatibant, deucrictibant and Compound 3 (the non-deuterated version of deucrictibant) are examples of competitive antagonists of the human B2 receptor, some of which having reached the stage of clinical trials. Other compounds structurally related to the common moiety, such as FR190997 and Compound 47a, are partial or nearly full agonists of the B2 receptor. The ongoing clinical development of deucrictibant for the treatment of hereditary angioedema is a first step in clarifying the therapeutic potential of orally bioavailable B2 receptor antagonists.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"195 ","pages":"Article 171466"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DR8 (DHNNPQIR), a rapeseed-derived peptide, mitigates fibrosis and muscle atrophy in chronic kidney disease by targeting CNR1–ERK/ELK-1 signaling","authors":"Wenli Zhang ,&nbsp;Yidan Zuo ,&nbsp;Diyan Xu ,&nbsp;Yibei Lin ,&nbsp;Yaoxue Zang ,&nbsp;Ruyi Chen ,&nbsp;Mingli Chen ,&nbsp;Zhen Su","doi":"10.1016/j.peptides.2025.171456","DOIUrl":"10.1016/j.peptides.2025.171456","url":null,"abstract":"<div><div>DR8 (DHNNPQIR) is a rapeseed-derived bioactive octapeptide with antioxidant and anti-inflammatory properties, but its therapeutic potential in chronic kidney disease (CKD) and related muscle wasting has not been defined. In this study, we investigated the anti-fibrotic and anti-atrophic efficacy of DR8 using complementary in vitro, transcriptomic, and in vivo approaches. In TGF-β1-stimulated C2C12 myoblasts and HK-2 tubular epithelial cells, DR8 significantly attenuated fibrosis and atrophy by downregulating cannabinoid receptor 1 (CNR1) and suppressing ERK-ELK1 activation, leading to restoration of myogenic regulators (MYOD, MYOG) and inhibition of proteolytic E3 ligases (MuRF-1, MAFbx). Transcriptomic analysis identified CNR1 as a key upstream target mediating these effects. In a 5/6 nephrectomized (5/6Nx) mouse model, systemic administration of DR8 significantly improved renal function, reduced collagen accumulation, and alleviated skeletal muscle fibrosis and atrophy, accompanied by suppression of CNR1-ERK-ELK1 activation in both organs. Together, these findings demonstrate that DR8 exerts strong renoprotective and myoprotective effects through selective modulation of CNR1-dependent signaling pathways, supporting its potential as a novel peptide therapeutic for CKD-associated fibrosis and muscle wasting.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171456"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}