Archives of biochemistry and biophysics最新文献

{"title":"The role of lncRNAs in sepsis-induced acute lung injury: Molecular mechanisms and therapeutic potential","authors":"Huijuan Qi,&nbsp;Gu Ying,&nbsp;Wang Ling,&nbsp;Honggang Jia,&nbsp;Xinxiu Zhou,&nbsp;Xinyu Lin","doi":"10.1016/j.abb.2025.110407","DOIUrl":"10.1016/j.abb.2025.110407","url":null,"abstract":"<div><div>Sepsis, a life-threatening syndrome, results from a dysregulated immune and hemostatic response, contributing to acute lung injury (ALI) and its progression into acute respiratory distress syndrome (ARDS). The development of septic ALI is complex, involving excessive inflammatory mediator production that damages endothelial and epithelial cells, leading to vascular leakage, edema, and vasodilation—key factors in ALI pathogenesis. Long noncoding RNAs (lncRNAs), over 200 nucleotides in length, play critical roles in various biological processes, including sepsis regulation. They exhibit both promotive and inhibitory effects, influencing sepsis progression and resolution. Despite their significance, comprehensive reviews detailing lncRNA involvement in sepsis-induced ALI remain limited. This review aims to address this gap by summarizing the diverse functions of lncRNAs in septic ALI, emphasizing their potential in diagnosis and treatment. Furthermore, we will explore the molecular mechanisms underlying lncRNA involvement, particularly their miRNA-dependent regulatory pathways. Understanding these interactions may provide novel insights into therapeutic strategies for sepsis-induced ALI.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110407"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased levels of Prx1 are associated with proteasome impairment and mitochondrial dysfunction in the yeast Saccharomyces cerevisiae","authors":"Natália Mori Avellaneda Penatti ,&nbsp;Mário Henrique Barros ,&nbsp;Fernando Gomes ,&nbsp;Luis Eduardo Soares Netto ,&nbsp;Kamila de Jesus Maciel ,&nbsp;Vincent Louis Viala ,&nbsp;Ana Mara Viana ,&nbsp;Marilene Demasi","doi":"10.1016/j.abb.2025.110406","DOIUrl":"10.1016/j.abb.2025.110406","url":null,"abstract":"<div><div>In previous studies we reported the S-glutathionylation at Cys residues (C76 and C221) of the α5 subunit of the 20S catalytic unit of the yeast proteasome, later mutated to Ser residues. Notably, the strain with the α5-C76S mutation exhibited a reduced chronological life span when grown in glucose as the carbon source. In the present study, we aimed to explore the interplay between mitochondria and the proteasome, considering the α5-C76S-mutated strain as a model of proteasomal impairment. For this purpose, we focused on the growth of the C76S strain in glycerol/ethanol as the carbon source. C76S strain exhibited poor growth and morphological alterations under these conditions, while the proteasomal activity was significantly decreased. We observed decreased activity of the 30S and 26S complexes in the C76S strain, which were accompanied by increased pool of poly-ubiquitinylated proteins. Regarding mitochondrial function, O₂ consumption and the concentration of total cellular ATP were significantly increased in the C76S strain. However, levels of peroxiredoxin-1 (Prx1), an important mitochondrial Cys-based peroxidase, were reduced in the C76S strain. In parallel, H₂O₂ release by mitochondrial respiration was augmented as well as decreased GSH/GSSG ratios, an important parameter of oxidative stress. These findings suggest that, despite increased O₂ consumption and ATP production, the mitochondria from the C76S strain promotes an increased oxidative stress most probably due to decreased Prx1 levels. DNA fragmentation and increased cytoplasmic cytochrome C, two apoptotic markers, were observed in the C76S strain. To assess the role of Prx1 in the survival of the C76S strain, we overexpressed this peroxiredoxin in both wild type and C76S strains, which resulted in the partial recovery of the C76S strain phenotype and proteasome activity. The relationship between decreased Prx1 concentration and proteasome impairment remains under investigation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110406"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosinase inhibition by natural stilbenoid glycosides: Critical role of the vinyl moiety in piceid for melanogenesis suppression","authors":"Yilu Sun,&nbsp;Jia Zhao,&nbsp;Jianhui Rong","doi":"10.1016/j.abb.2025.110405","DOIUrl":"10.1016/j.abb.2025.110405","url":null,"abstract":"<div><div>Skin hyperpigmentation due to UV-induced tyrosinase activation and melanin overproduction is an ongoing challenge in cosmetic and dermatological applications. While resveratrol analogues show anti-melanogenic potential, the structure-activity relationships of their glycosylated derivatives remain underexplored. Here, we investigate how the vinyl moiety in the food-derived stilbenoid glycoside piceid (resveratrol-3-<em>O</em>-β-glucoside) affects tyrosinase inhibition. We reduced the vinyl moiety to yield dihydropiceid by catalytic hydrogenation and systematically assessed both compounds for anti-melanogenic effects. As results, piceid exhibited superior monophenolase inhibition over dihydropiceid in enzyme kinetics, while both compounds showed comparable diphenolase inhibition. Cellular assays revealed that piceid reduced melanin production by 59.2 % at 25 μM in α-MSH-stimulated B16F10 melanoma cells, whereas dihydropiceid showed weaker activity (&lt;25 % reduction). MolgpKa analysis indicated that the vinyl moiety lowered the 4′-OH pKa (9.7 vs. 9.9), while UV–vis spectroscopy validated that the vinyl moiety enhanced the copper chelation capacity of piceid (ΔOD: 0.459) over dihydropiceid (ΔOD: 0.233). Molecular docking revealed that 4′-OH in piceid closely coordinated the tyrosinase binuclear copper center, whereas molecular dynamics simulation validated that hydrogen bonding supports the binding of both compounds to tyrosinase. Collectively, this study establishes the vinyl moiety in dietary stilbenoids as a critical pharmacophore for tyrosinase inhibition and thereby provides a molecular basis for developing natural anti-hyperpigmentation functional foods or cosmeceuticals.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110405"},"PeriodicalIF":3.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Cucurbitacin B inhibits gastric cancer progression by suppressing STAT3 activity\" [Archiv. Biochem. Biophys. 684 (2020) 108314].","authors":"Jiaixin Xu, Yunhe Chen, Rui Yang, Tong Zhou, Wei Ke, Yuan Si, Shusheng Yang, Te Zhang, Xuewen Liu, Liang Zhang, Ke Xiang, Yang Guo, Ying Liu","doi":"10.1016/j.abb.2025.110401","DOIUrl":"10.1016/j.abb.2025.110401","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110401"},"PeriodicalIF":3.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The odorant (R)-(-)-carvone promotes glucose-stimulated insulin secretion via the olfactory receptor Olfr1259 in pancreatic β-TC6 cells","authors":"Shi-Meng Gong ,&nbsp;Yangwei Jiang ,&nbsp;Yan-Bo Xue ,&nbsp;Yuan-Yuan Peng ,&nbsp;Chun-Yan Qian ,&nbsp;Yue Zhang ,&nbsp;Ruhong Zhou ,&nbsp;Liquan Huang","doi":"10.1016/j.abb.2025.110404","DOIUrl":"10.1016/j.abb.2025.110404","url":null,"abstract":"<div><div>Olfactory receptors (ORs) make up the largest subfamily of G protein-coupled receptors that are expressed in olfactory sensory neurons in the nasal cavity and recognize an enormous number of odorants from the external environment. These receptors, however, have also been found in many other tissues including pancreas, liver, and adipose tissue, in which they seem to play important but different roles. Yet, the exact functions of ORs in these extra-nasal tissues are not well understood. Here, we report that (R)-(-)-carvone and a few other odorants were able to evoke calcium responses in mouse pancreatic β-TC6 cells. Furthermore, (R)-(-)-carvone potentiated cytoplasmic cAMP accumulation and glucose-stimulated insulin secretion (GSIS). More importantly, GPCR signaling pathway components adenylyl cyclase, phospholipase C, and inositol triphosphate receptor were involved in (R)-(-)-carvone-induced signal transduction. By reanalyzing the available β-TC6 cells’ RNAseq dataset, we identified several candidate ORs for (R)-(-)-carvone. Further analyses with molecular docking and molecular dynamics simulations indicated that (R)-(-)-carvone bound to the odorant-binding pocket of the olfactory receptor Olfr1259 while knockdown of Olfr1259 expression in β-TC6 cells with siRNA significantly reduced the stimulatory effects of (R)-(-)-carvone on cytoplasmic Ca²⁺ and cAMP levels, and insulin secretion. Together, these results indicated that Olfr1259 is the receptor for (R)-(-)-carvone in β-TC6 cells. Therefore, our study highlighted the important roles of (R)-(-)-carvone and its receptor Olfr1259 in initiating calcium signaling, inducing intracellular cAMP accumulation, and enhancing GSIS in pancreatic β cells, demonstrating that Olfr1259 may be a new therapeutic target for regulating glucose metabolism and for treating diabetes.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110404"},"PeriodicalIF":3.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging oligomers of alpha-toxin (Hla) variants using high-speed AFM and neutralizing Hla hemolytic activity with their antisera","authors":"Ngan Thi Phuong Le ,&nbsp;Kien Xuan Ngo ,&nbsp;Trinh Thi Ngoc Nguyen ,&nbsp;Linh-Thuoc Tran ,&nbsp;Hoang Duc Nguyen","doi":"10.1016/j.abb.2025.110403","DOIUrl":"10.1016/j.abb.2025.110403","url":null,"abstract":"<div><div>Alpha-toxin (Hla) variants, such as the toxoids HlaH35A, HlaH35L, and HlaH35LH48L, have been shown to lack hemolytic activity and present promising antigen sources for vaccine development against <em>S. aureus</em>. The His35 site is critical in the oligomerization process of Hla during transmembrane pore formation, leading to cell lysis. This study employed high-speed atomic force microscopy (HS-AFM) to image the structures of HlaH35A, HlaH35L, and HlaH35LH48L proteins on POPC/Chol lipid membranes. Single-site His35 mutations (HlaH35A, HlaH35L) could form oligomer structures, whereas the double-site HlaH35LH48L mutation resulted in the monomer state. These HS-AFM findings confirm that the region between His35 and His48 is crucial for protomer-protomer interactions essential for oligomerization and pore formation. Hemolytic activity of wild-type Hla on red blood cells (RBCs) was significantly reduced when mixed with HlaH35A, HlaH35L, or HlaH35LH48L at weight ratios 1:5 (HlaWT:toxoid) or higher. However, these toxoids exhibited weak neutralization activities at lower mixing ratios with HlaWT. The increased anti-Hla antibodies (IgG) in mice treated with these Hla toxoids have emerged as a potential treatment avenue to neutralize the hemolytic activity of the HlaWT toxin on RBCs. Serum analysis from mice injected with HlaH35A, HlaH35L, and HlaH35LH48L toxoids showed that these sera could neutralize the hemolytic activity of the HlaWT toxin. Thus, these Hla variants are promising candidates for developing supportive treatments for <em>S. aureus</em> infections.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110403"},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and dynamics of Proteus vulgaris tryptophan indole-lyase complexes with l-ethionine and l-alanine","authors":"Robert S. Phillips ,&nbsp;S. Meredith Brown","doi":"10.1016/j.abb.2025.110402","DOIUrl":"10.1016/j.abb.2025.110402","url":null,"abstract":"<div><div>Tryptophan indole-lyase (TIL; [E.C. 4.1.99.1]) is a pyridoxal-5′-phosphate (PLP) dependent enzyme that catalyzes the reversible β-elimination of indole from <span>l</span>-tryptophan. <span>l</span>-Alanine and <span>l</span>-ethionine are TIL competitive inhibitors that form stable quinonoid complexes with <em>λ_max</em> ∼508 nm. We have now determined the X-ray crystal structure of the tetrameric TIL complexes with <span>l</span>-alanine and <span>l</span>-ethionine, with either K⁺ or Na⁺ in the cation binding site. For the K⁺-form, the structures show a mixture of external aldimine and quinonoid complexes, with both open and closed active site conformations. However, the Na⁺-form exhibits noncovalent and external aldimine complexes in only open active site conformations. Stopped-flow kinetics of <span>l</span>-ethionine binding show that the Na⁺-form of TIL reacts much more slowly than the K⁺-form. The <span>l</span>-alanine and <span>l</span>-ethionine complexes of TIL are affected by hydrostatic pressure, suggesting that solvation contributes to the reaction. As pressure increases, the peak at 508 nm decreases, and a new peak at 344 nm appears. These changes are reversible when pressure is released. The 344 nm species could be either a <em>gem</em>-diamine or an enolimine tautomer of the external aldimine. We measured the fluorescence spectrum of the complex under pressure to differentiate these structures. When excited at either 290 or 325 nm, the complex emits at 400 nm, establishing that it is a <em>gem</em>-diamine complex. This peak does not form when the Na⁺-form of TIL complexed with <span>l</span>-ethionine is subjected to high pressure. Pressure jumps for the TIL-K⁺-<span>l</span>-ethionine complex measured at 508 nm result in pressure dependent relaxation rate constants. The relaxations show a large activation volume in the direction of quinonoid intermediate formation, suggesting that it is coupled with a conformational change. These results provide new insights into the dynamics of ligand binding to TIL.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110402"},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSPB1 suppresses oxLDL-induced vascular smooth muscle cell ferroptosis by inhibiting DPP4","authors":"Yi Li ,&nbsp;Lijun Zhang ,&nbsp;Qi Zhang ,&nbsp;Yuke Zhang ,&nbsp;Shuang Pan ,&nbsp;Huanhuan Zhao ,&nbsp;Lijun Zhang","doi":"10.1016/j.abb.2025.110400","DOIUrl":"10.1016/j.abb.2025.110400","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis is the major pathological basis of cardiovascular diseases. Vascular smooth muscle cell (VSMC) dysfunction and death induced by oxidized low-density lipoprotein (oxLDL) play a key role in atherosclerosis. Ferroptosis is a novel iron-dependent lipid peroxidation regulated cell death, which is implicated in atherosclerosis. However, whether oxLDL induces VSMC ferroptosis and the specific mechanism is unclear.</div></div><div><h3>Methods</h3><div>To determine the effects of oxLDL on VSMC ferroptosis, LDH activity, MDA and Fe²⁺ content, glutathione peroxidase 4 (GPX4) expression and GPX enzyme activity were assayed. The level of lipid peroxidation was detected by C11 BODIPY fluorescence staining. RT-qPCR and Western blot were used to detect the mRNA and protein expressions of heat shock protein B1 (HSPB1), dipeptidyl peptidase 4 (DPP4) and nuclear factor kappa-B (NF-κB). The siRNAs, plasmids and Val-boropro were utilized to explore the roles of HSPB1/NF-κB/DPP4 in oxLDL-induced VSMC ferroptosis.</div></div><div><h3>Results</h3><div>oxLDL increased LDH activity, Fe²⁺ content, lipid peroxidation and MDA content in VSMCs, which were inhibited by ferroptosis inhibitors Lip-1 and DFO. Moreover, oxLDL reduced GPX4 protein expression and GPX enzyme activity, indicating that oxLDL induces VSMC ferroptosis. Notably, HSPB1 inhibited oxLDL-induced VSMC ferroptosis by reducing the accumulation of Fe²⁺ and lipid peroxidation and increasing GPX4 expression and activity. In addition, HSPB1 suppressed oxLDL-induced VSMC ferroptosis by inhibiting DPP4 through NF-κB. Furthermore, Val-boropro could rescue oxLDL-induced ferroptosis in VSMCs with HSPB1 knockdown by inhibiting DPP4.</div></div><div><h3>Conclusions</h3><div>This study reveals for the first time that HSPB1 suppresses oxLDL-induced VSMC ferroptosis by inhibiting DPP4 through NF-κB, providing new strategies for the prevention and treatment of atherosclerosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110400"},"PeriodicalIF":3.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UCP2 attenuates neural apoptosis and inflammation in spinal cord injury by inducing the acetylation of ANXA1 and activating the PI3K/AKT pathway","authors":"Guolin Zhu,&nbsp;Junjie Li,&nbsp;Jinxin Luo,&nbsp;Yaojian Rao","doi":"10.1016/j.abb.2025.110399","DOIUrl":"10.1016/j.abb.2025.110399","url":null,"abstract":"<div><div>Spinal cord injury (SCI) represents a prevalent form of mechanical trauma, frequently resulting in significant disability and mortality. Uncoupling protein 2 (UCP2) has been recognized for its neuroprotective properties; however, its specific role in SCI remains to be elucidated. This study aims to investigate the neuroprotective effects of UCP2 in the context of SCI and to further explore its downstream mechanisms of action. Through <em>in vitro</em> experiments, we demonstrated that UCP2 overexpression significantly improved cell viability and inhibited apoptosis and inflammatory responses in the lipopolysaccharides (LPS)-induced SCI cell model. Results of animal experiments showed that adeno-associated virus-mediated overexpression of UCP2 contributed to the recovery of SCI-afflicted rats, evidenced by improved Basso, Beattie, and Bresnahan scores, decreased water content in spinal tissues, reduced number of apoptotic cells in spinal cord. Mechanistic investigations revealed that UCP2 directly interacts with annexin A1 (ANXA1), enhancing its protein stability through acetylation at the K58 site. Furthermore, UCP2 was found to activate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway by upregulating ANXA1 expression. Rescue assays indicated that knockdown of ANXA1 or inactivation of the PI3K/AKT pathway by LY294002 treatment partially neutralized the protective effects of UCP2 overexpression against apoptosis and inflammatory responses in LPS-stimulated BV-2 cells. Taken together, this study concludes that UCP2 ameliorates apoptosis and inflammatory responses in the SCI model by modulating acetylation-mediated protein stabilization of ANXA1 and activating the PI3K/AKT pathway.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110399"},"PeriodicalIF":3.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-200 family: Gatekeepers of fibrinolytic regulation in lung pathologies during acute lung injury","authors":"T.M. Jeena ,&nbsp;C. Rakshitha ,&nbsp;Fathimath M Muneesa ,&nbsp;Aleena Varughese ,&nbsp;Akarsha ,&nbsp;Rajesh Raju ,&nbsp;Deepak Krishnan ,&nbsp;Kirana Mugaranja ,&nbsp;Yashodhar P. Bhandary","doi":"10.1016/j.abb.2025.110398","DOIUrl":"10.1016/j.abb.2025.110398","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a severe condition characterized by acute inflammation and respiratory distress, often leading to significant morbidity and mortality. The complex pathophysiology of ALI involves alterations in various molecular and cellular processes, including those regulated by the miR-200 family. This study aims to investigate the regulatory function of miR-200 family members on the fibrinolytic system using three different agents: Bleomycin, IL-17A, and TGF-β, in both <em>in vitro</em> (A549 cells) and <em>in vivo</em> (C57BL/6 mice) models.</div><div>The role of miR-200a and miR-200b in modulating the fibrinolytic system was assessed through mRNA and protein expression analyses. The results show that in both <em>in vitro</em> and <em>in vivo</em> models, treatment with miR-200a and miR-200b mimics greatly reduced the abnormalities caused by the three drugs. Treatments were given during the inflammatory phase of ALI at two different time points for the <em>in vivo</em> studies: 3 and 7 days. This was evidenced by increased uPA and uPAR mRNA levels and decreased PAI-1 mRNA and protein expression. The inverse regulatory roles of miR-200 family members, particularly miR-200a and miR-200b, suggest potential therapeutic targets in ALI.</div><div>Furthermore, our study highlights how IL-17A and TGF-β modulate the fibrinolytic system and EMT pathway by influencing the expression of the miR-200 family in ALI. It elucidates the regulatory function of the miR-200 family in restoring the fibrinolytic system and the EMT pathway during lung injury, underscoring the significant therapeutic potential of miR-200 in treating ALI.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"768 ","pages":"Article 110398"},"PeriodicalIF":3.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}