Folia histochemica et cytobiologica最新文献

{"title":"Tectochrysin suppresses the profibrotic phenotype of human keloid fibroblasts and is associated with reduced nuclear p65 accumulation.","authors":"Lin Ma, Wei Zheng, Weibo Song, Aijing Ma, Qianqian Zhang, Lei Gao, Hongyu Wang","doi":"10.5603/fhc.111687","DOIUrl":"10.5603/fhc.111687","url":null,"abstract":"<p><strong>Introduction: </strong>Keloids are fibroproliferative scars characterized by persistent fibroblast activation and excessive extracellular matrix deposition. Tectochrysin is a natural flavone with anti-inflammatory and anti-oxidative activities, but its effects on keloid fibroblasts remain unclear.</p><p><strong>Material and methods: </strong>Human keloid fibroblasts (HKFs) and human skin fibroblasts (HSFs) were exposed to tectochrysin. Cell viability was assessed by CCK-8. HKF apoptosis, intracellular reactive oxygen species (ROS), wound closure, vimentin immunofluorescence, profibrotic protein expression, and nuclear/cytoplasmic p65 distribution were evaluated. TGF-β1-stimulated HSFs were used as a controllable profibrotic activation model.</p><p><strong>Results: </strong>Tectochrysin preferentially decreased HKF viability at 5 and 10 μg/mL while exerting weaker effects on HSFs, and significantly increased HKF apoptosis. It reduced intracellular ROS, delayed wound closure, altered vimentin-positive cytoskeletal organization in adherent HKFs, and decreased α-smooth-muscle-actin, collagen I, and fibronectin expression in HKFs. Tectochrysin also attenuated TGF-β1-induced upregulation of these markers in HSFs. Nuclear p65 abundance was reduced, whereas cytoplasmic p65 changed only modestly.</p><p><strong>Conclusions: </strong>Tectochrysin suppresses the profibrotic phenotype of keloid fibroblasts and is associated with reduced nuclear p65 accumulation, supporting further evaluation as a candidate anti-keloid agent.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"140-149"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Professor Tadeusz Cichocki (1936-2026).","authors":"Jan A Litwin","doi":"10.5603/fhc.115038","DOIUrl":"https://doi.org/10.5603/fhc.115038","url":null,"abstract":"","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"64 3","pages":"165"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSSC3 as a potential biomarker in osteosarcoma: implications for angiogenesis.","authors":"Hanzhen Feng, Wenmang Xu, Qiang Feng, Xiaolong Wei, Meijin Huang, Ziran Gao","doi":"10.5603/fhc.112768","DOIUrl":"10.5603/fhc.112768","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma (OS) is a highly vascularized malignant tumor whose growth and metastasis depend on angiogenesis. Tumor-suppressing STF cDNA 3 (TSSC3) has been identified as a tumor suppressor in OS, but its role and underlying mechanisms in regulating angiogenesis remain unclear.</p><p><strong>Material and methods: </strong>Immunohistochemistry was used to assess the expression of TSSC3, VEGF-A, and CD31 in OS tissues. OS cells that stably overexpressed TSSC3 were established via lentiviral transduction, and conditioned medium from these cells was used to culture human umbilical vein endothelial cells (HUVECs). The proliferation, migration, and tube formation of HUVECs were evaluated using CCK-8, wound healing, Transwell, and tube formation assays. qRT-PCR and Western blotting were conducted to assess VEGFA mRNA and VEGF-A protein levels in TSSC3-overexpressing cells. A xenograft model in nude mice was used to evaluate angiogenesis in vivo, and changes in the Src/ERK pathway were examined by Western blotting.</p><p><strong>Results: </strong>TSSC3 was downregulated, and VEGF-A was upregulated in OS tissues, both of which were associated with prognosis. Conditioned medium from the TSSC3-overexpressing cells significantly inhibited HUVEC proliferation, migration, and tube formation. In vivo, TSSC3 overexpression led to reduced tumor weight, VEGF-A expression, and microvessel density. Moreover, TSSC3 suppressed VEGF-A synthesis and secretion in a Src/ERK-dependent manner.</p><p><strong>Conclusions: </strong>TSSC3 inhibits angiogenesis in OS by downregulating VEGF-A via the Src/ERK pathway, providing a theoretical and experimental basis for anti-angiogenic therapies targeting TSSC3.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"183-195"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg3 inhibits Ang II-induced cardiac fibrosis via the GLP-1 receptor signaling pathway.","authors":"Jie Zhao, Zheng Yan, Chaokun Guan, Dongsheng Li, Xisheng Yan, Xiao Li, Yanglin Li, Xing Liu, Shifan Tang","doi":"10.5603/fhc.106697","DOIUrl":"10.5603/fhc.106697","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac fibrosis is a major pathological feature of multiple cardiovascular diseases and an important risk factor for heart failure. Ginsenoside Rg3 (Rg3), a natural triterpenoid saponin extracted from Panax ginseng, has been shown to exert cardioprotective effects. In this study, we assessed the effects of Rg3 on angiotensin II (Ang II)-induced cardiac fibrosis in both cellular and animal models and investigated the underlying mechanisms.</p><p><strong>Material and methods: </strong>For the cellular experiments, primary mouse cardiac fibroblasts (CFs) were treated with Ang II (1 μM) and Rg3 (25, 50, or 100 μM) for 24 h to assess the effects of Rg3 on cardiac fibrosis in vitro. The glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin-3 (9-39) (1 μM) was used to validate the role of GLP-1R signaling in the anti-fibrotic effects of Rg3 in vitro. A CCK-8 assay was performed to assess cell viability. For the animal experiments, male C57BL/6J mice were divided into 4 groups (6 mice per group): Sham, Ang II, Ang II + Rg3 (50 mg/kg), and Ang II + Rg3 (100 mg/kg). Collagen deposition in mouse cardiac tissues was assessed by picrosirius red staining. The expression of fibrosis-related proteins (MMP-2, MMP-9, α-SMA, collagen I, collagen III, and fibronectin), GLP-1R, phosphorylated Smad2/3, total Smad2/3, RhoA, and ROCK2 in CFs and mouse cardiac tissues was examined by RT-qPCR, western blotting, and immunofluorescence staining.</p><p><strong>Results: </strong>Rg3 treatment reversed the Ang II-induced upregulation of MMP-2, MMP-9, α-SMA, collagen I, collagen III, p-Smad2/3, RhoA, and ROCK2 and the downregulation of GLP-1R in CFs. Exendin-3 (9-39) antagonized the effects of Rg3 on the expression of fibrosis-related proteins, GLP-1R, p-Smad2/3, RhoA, and ROCK2 in CFs. Furthermore, Rg3 administration suppressed collagen deposition, reduced the expression of MMP-2, MMP-9, α-SMA, collagen I, collagen III, p-Smad2/3, RhoA, and ROCK2, and increased GLP-1R levels in the cardiac tissues of Ang II-infused mice.</p><p><strong>Conclusions: </strong>Rg3 exerts an anti-fibrotic effect in cardiac fibrosis models by inhibiting activation of the RhoA/ROCK and Smad2/3 pathways through upregulation of GLP-1R.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"60-74"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling.","authors":"Dan Wei, Peng-Li Wang, Jing Jiang","doi":"10.5603/fhc.110087","DOIUrl":"10.5603/fhc.110087","url":null,"abstract":"<p><strong>Introduction: </strong>Lactucin, a sesquiterpene lactone isolated from chicory (Cichorium intybus L.), demonstrates broad-spectrum anticancer activity across multiple malignancies, yet its mechanistic role in gastric cancer (GC) remains unexplored. This study aimed to elucidate the potential mechanism by which lactucin modulates GC cell proliferation and apoptosis.</p><p><strong>Material and methods: </strong>NUGC-3 and MKN-1 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for animal studies. To assess cell proliferation, cell cycle distribution, and apoptosis, CCK-8 assay and flow cytometry analyses were conducted, while cell morphology was examined under an inverted microscope. Levels of proteins associated with cell cycle, apoptosis, and mitogen-activated protein kinase (MAPK) signaling were determined by Western blotting.</p><p><strong>Results: </strong>In vitro, lactucin significantly attenuated GC cell proliferation and induced alterations in their morphology. Lactucin induced cell cycle arrest in the G0/G1 phase by reducing protein levels of cyclins (cyclin B1 and cyclin D1) and cyclin-dependent kinases (CDKs), including CDK2 and CDK4. Moreover, lactucin promoted GC cell apoptosis in a dose-dependent manner by downregulating Bcl-2, upregulating Bax, and increasing cleavage of caspase-3 and PARP. In vivo, lactucin inhibited tumor growth and decreased Ki67 expression levels in xenograft tumors.</p><p><strong>Conclusions: </strong>Lactucin inhibited proliferation, induced cell cycle arrest and apoptosis in GC cells by inactivating the MAPK/p38 pathway.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"89-98"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SIRT2-mediated mitophagy to enhance ferroptosis: a novel mechanism of berberine action in non-small cell lung cancer.","authors":"Mingliang Wu, Guobiao Yang, Jianye Yang, Mengmin Xu","doi":"10.5603/fhc.112068","DOIUrl":"10.5603/fhc.112068","url":null,"abstract":"<p><strong>Introduction: </strong>Berberine (BBR), a natural isoquinoline alkaloid, has been shown to specifically bind to sirtuin 2 (SIRT2) and exhibit anticancer activity. This study aimed to elucidate the therapeutic mechanisms of BBR in non-small cell lung cancer (NSCLC).</p><p><strong>Material and methods: </strong>A murine xenograft tumor model of NSCLC was established. Hematoxylin and eosin (H&E) staining and immunohistochemistry were employed to evaluate the therapeutic efficacy of BBR in vivo. In vitro, H1975 cells were treated with BBR to assess cell viability and migration. H1975 cells were transfected with lentivirus carrying sh-SIRT2 constructs to knock down SIRT2 expression. Ferroptosis was evaluated by measuring malondialdehyde (MDA), glutathione (GSH), and iron (Fe2+) levels. Protein expression levels of SIRT2, ferroptosis markers, and mitophagy markers were analyzed by Western blotting. Mitophagy was also assessed by the colocalization of TOMM20 and LAMP1 using immunofluorescence.</p><p><strong>Results: </strong>BBR inhibited NSCLC progression both in vivo and in vitro, accompanied by upregulated SIRT2 expression. Mechanistically, BBR induced mitophagy and ferroptosis, as evidenced by increased Fe2+ and MDA levels, decreased GSH content, downregulation of GPX4 and SLC7A11, increased protein levels of PINK1 and Parkin, and increased fluorescence colocalization of TOMM20 and LAMP1. Silencing of SIRT2 attenuated BBR-induced suppression of H1975 cell viability and promotion of ferroptosis in a mitophagy-dependent manner. Treatment with a mitophagy activator reversed the effects of sh-SIRT2 and restored the therapeutic efficacy of BBR.</p><p><strong>Conclusions: </strong>The SIRT2/mitophagy/ferroptosis axis represents a key mechanism underlying the anti-NSCLC activity of BBR.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"210-220"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal Lnc-DLK1-35 reprograms microglia into a pro-tumorigenic phenotype via a non-canonical cytokine signature to promote glioblastoma progression and chemoresistance.","authors":"Dan Li, Yufeng Li, Zhuo Wang, Xuan Zheng, Yang Wang, Jianxiong Guo, Jingwu Li, Yongliang Liu, Yuhui Li","doi":"10.5603/fhc.109684","DOIUrl":"10.5603/fhc.109684","url":null,"abstract":"<p><strong>Introduction: </strong>Temozolomide (TMZ) resistance in glioblastoma (GBM) involves dynamic crosstalk of cancer cells with tumor-associated microglia, but the role of exosomal long non-coding RNAs (lncRNAs) remains poorly defined.</p><p><strong>Material and methods: </strong>We isolated exosomes from TMZ-sensitive (U251) and TMZ-resistant (U251TR) GBM cells. Lnc-DLK1-35 expression was modulated by overexpression/knockdown and validated by RT-qPCR. Exosome internalization by microglia (HMC3 cells) was tracked via PKH67 labeling. Microglial polarization was assessed by studying morphology, marker expression (CD16/CD32/iNOS/Arg-1/CD206/CD163), and cytokine secretion (ELISA: IL-6, TNF-α, TGF-β, IL-10, CXCL13). Functional impact on GBM cells by indirect co-culture with IL4-activated HMC3 cells was examined using CCK-8 and Transwell assays.</p><p><strong>Results: </strong>Lnc-DLK1-35 was enriched in U251TR cells and their exosomes. GBM exosomes delivered Lnc-DLK1-35 to microglia, inducing a unique GBM-educated phenotype: amoeboid morphology, elevated type 1 macrophage (M1) markers (CD16, iNOS) but suppressed immunoregulatory factors (IL-10, CXCL13). This reprogramming required exosomal transfer. In addition, indirect co-culture with IL4-activated HMC3 cells enhanced GBM malignancy, reduced TMZ sensitivity and promoted migration and invasion.</p><p><strong>Conclusions: </strong>Exosomal Lnc-DLK1-35 reprograms cultured microglia cells into a pro-tumorigenic state via a non-canonical cytokine signature, driving TMZ resistance and invasion. Targeting this axis disrupts microglia-GBM communication, revealing a novel therapeutic strategy.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"48-59"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of BDNF-TrkB-AKT1 pathway components and apoptosis-related factors across yak brain regions at low and high altitudes.","authors":"Qian Zhang, Yan Cui, Junfeng He, Yangyang Pan, Meng Wang, Hongliang Jin","doi":"10.5603/fhc.110409","DOIUrl":"10.5603/fhc.110409","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different altitudes.</p><p><strong>Material and methods: </strong>The cerebral cortex, cerebellum, hippocampus, thalamus, and medulla oblongata were collected from 3-year-old yaks living at low and high altitudes. The relative mRNA expression of BDNF, TrkB, AKT1, Bcl-2, and Bax was assessed by qRT-PCR. Protein abundance and cellular localization of BDNF, TrkB, AKT1, Bcl-2, and Bax were evaluated by Western blotting and immunohistochemistry, with immunoreactivity quantified by optical density analysis.</p><p><strong>Results: </strong>Within each altitude group, BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and the corresponding protein levels (BDNF, TrkB, AKT1, and Bcl-2) were significantly higher in the cerebral cortex and hippocampus than in the cerebellum, thalamus, and medulla oblongata (P < 0.05). In contrast, Bax mRNA and Bax protein levels did not differ significantly among the five regions. Compared with low-altitude yaks, high-altitude yaks showed significantly higher BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and higher BDNF, TrkB, AKT1, and Bcl-2 protein levels in brain tissues (P < 0.05), whereas Bax protein expression did not differ between altitude groups. Immunohistochemistry revealed immunoreactivity for BDNF, TrkB, AKT1, Bcl-2, and Bax in both altitude groups, with prominent labeling in cortical pyramidal neurons and across the pyramidal cell layer in the hippocampal CA region. Immunoreactivity was also detected in large neurons of the thalamus and medulla oblongata. In the cerebellum, labeling was strongest in Purkinje cells, with weaker signals in the granule cell layer and molecular layer.</p><p><strong>Conclusions: </strong>BDNF-TrkB-AKT1 pathway components and Bcl-2 showed relatively higher expression in the cerebral cortex and hippocampus within each altitude group, whereas Bax expression did not vary across regions. These patterns are consistent with an association between BDNF-TrkB-AKT1 signaling and increased Bcl-2 expression without a corresponding increase in Bax, which may support neuronal adaptation in the cerebral cortex and hippocampus. Elevated expression of BDNF, TrkB, AKT1, and Bcl-2 at high altitude suggests enhanced adaptation to hypoxia in high-altitude yaks; the underlying mechanisms require further investigation.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"39-47"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splenic fibrosis markers in rats with portal vein stenosis.","authors":"Zhao Bo, Jingtong Li, Hongliang Zhang, Jiaqi Lu, Yuxu Zhong, Haibo Chu, Yongbo Xu, Tao Liu","doi":"10.5603/fhc.114318","DOIUrl":"10.5603/fhc.114318","url":null,"abstract":"<p><strong>Introduction: </strong>Congestive splenomegaly (SM) secondary to portal hypertension refers to pathological splenic enlargement caused by elevated portal venous pressure; however, the molecular mechanisms underlying splenic fibrosis remain incompletely understood.</p><p><strong>Material and methods: </strong>This study established a portal vein stenosis-induced model of SM in Sprague-Dawley rats (SM group, n = 20), with a sham-operated control (SO) group (n = 20). Splenic tissue fibrosis was evaluated using special staining techniques, including Masson's trichrome, Elastica van Gieson, and ammoniacal silver staining. Matrix metallopeptidase 2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, transforming growth factor beta 1 (TGF-β1), and mothers against decapentaplegic homolog 7 (Smad7) were assessed using immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting.</p><p><strong>Results: </strong>In the SM group, microscopic examination revealed diffuse collagen proliferation, elastic fiber fragmentation, and reticular fiber densification. The proportions of MMP-2-, MMP-9-, TIMP-1-, TIMP-2-, TGF-β1-, and Smad7-positive cells were significantly higher than those in the SO group (P < 0.001). The mRNA expression levels of MMP-2, MMP-9, TIMP-1, TIMP-2, TGF-β1, and Smad7 were also significantly higher than in the SO group (P < 0.001). Protein expression levels of MMP-2, MMP-9, and Smad7 were significantly higher in the SM group than in the SO group (P < 0.001).</p><p><strong>Conclusions: </strong>In a rat model of portal hypertension, our findings suggest that MMP/TIMP imbalance and TGF-β1-Smad7 signaling are involved in splenic fibrosis, highlighting the TGF-β1/Smad7 axis as a potential therapeutic target for attenuating splenic fibrotic remodeling.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"221-232"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis.","authors":"Malgorzata Blatkiewicz, Kacper Kaminski, Marta Sobalska-Kwapis, Marta Szyszka, Anna Olechnowicz, Karol Jopek, Marcin Rucinski","doi":"10.5603/fhc.110668","DOIUrl":"10.5603/fhc.110668","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c), a 16-amino acid mitochondrial-derived peptide, regulates cellular metabolism through AMPK and mTOR signaling and exerts protective effects across multiple endocrine tissues. However, its role in adrenal physiology remains unexplored. We hypothesized that MOTS-c establishes \"steroidogenic readiness\" by priming metabolic pathways rather than directly activating hormone synthesis.</p><p><strong>Material and methods: </strong>Adult male Wistar rats (n = 16) received continuous MOTS-c (0.1 μmol/24 h) or saline via subcutaneous micro-osmotic pumps for 24 hours. Adrenal tissues were analyzed using qRT-PCR, immunohistochemistry, ELISA, and RNA-sequencing.</p><p><strong>Results: </strong>MOTS-c showed significantly higher expression in ZF/ZR vs. ZG. MOTS-c treatment did not alter classical steroidogenic genes or circulating corticosterone and aldosterone levels. RNA-seq identified 39 differentially expressed genes, notably upregulation of purinergic receptor P2ry4 (4.3-fold, P < 0.05) - a novel MOTS-C target enhancing calcium signaling. Additional changes included upregulation of Apoc4 and downregulation of stress markers Bag3 and Smurf2, mitochondrial carrier Slc25a30, and peroxisomal factor Pex11a. Gene Set Enrichment Analysis revealed inhibition of cAMP response, mitophagy, and histone deacetylation pathways, alongside activation of cell proliferation, indicating metabolic reprogramming without steroidogenic activation.</p><p><strong>Conclusions: </strong>MOTS-c functions as a metabolic conductor that primes adrenocortical cells for enhanced steroidogenic responsiveness without stimulating basal hormone synthesis. By upregulating calcium signaling, modulating lipid metabolism, downregulating stress-response proteins, and inhibiting mitophagy, MOTS-c establishes a preparatory metabolic state optimized for subsequent ACTH or stress stimulation. These findings reveal a novel preparatory mechanism in adrenal physiology and identify MOTS-c as a potential therapeutic target for HPA axis disorders requiring enhanced adrenal reserve capacity without basal hypercortisolemia.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"26-38"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}