Cell Biology and Toxicology最新文献

{"title":"The role of e3 ubiquitin ligases and deubiquitinating enzymes in hepatocellular carcinoma.","authors":"Lei Wang, Hongyan Zhang, Yue Hu, Xingqiang Li, Jing Liu, Ying Liang","doi":"10.1007/s10565-026-10192-1","DOIUrl":"https://doi.org/10.1007/s10565-026-10192-1","url":null,"abstract":"<p><p>Ubiquitination, a key post-translational modification, is responsible for regulating protein stability, activity, subcellular localization, and interactions via the ubiquitin-proteasome system (UPS). The UPS plays a role in non-lysosomal protein degradation, involved in the coordinated action of ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). The review elaborates on the functions of key E3 ligases of MDM2, β-TrCP, and SCF complexes, which modulate cell cycle progression, apoptosis, metabolic reprogramming, and drug resistance in hepatocellular carcinoma (HCC). For instance, MDM2 promotes HCC development by degrading the tumor suppressor p53, while β-TrCP influences the Wnt/β-catenin signaling axis by changing β-catenin levels. Deubiquitinating enzymes (DUBs), including the USP family and CYLD, also play significant roles in HCC by stabilizing or destabilizing critical proteins involved in oncogenesis. The clinical potential of ubiquitination-related molecules as biomarkers for predicting HCC prognosis and as therapeutic targets is also discussed. This review comprehensively examines the role of ubiquitination modification in HCC and its clinical relevance. Future research directions include the exploration of novel ubiquitination modifications, their interactions with other post-translational modifications, and the development of precision medicine strategies based on multi-omics technologies to improve HCC treatment outcomes.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Troxerutin suppresses the stemness of hepatocellular carcinoma via the Syk/FOXO3 feedback loop.","authors":"Shan Liu, Yuan Lin, Huan Xia, Hanhan Li, Yan Dou, Jiamin Luo, Tiantian Yang, Qi Zeng, Wei Guo, Hanrui Chen","doi":"10.1007/s10565-026-10194-z","DOIUrl":"https://doi.org/10.1007/s10565-026-10194-z","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains one of the deadliest malignancies worldwide due to its high rates of recurrence and metastasis. This underscores the urgent need to develop innovative drugs and treatment strategies to improve patient outcomes. This study examined the molecular pathways underlying troxerutin's therapeutic potential in HCC, providing information that could aid in the development of novel therapeutic strategies. Cell proliferation and apoptosis were assessed using CCK-8, EdU assays, and flow cytometry. Protein expression and mRNA alterations were analyzed by Western blotting and PCR, respectively. Cell migration and invasion were evaluated using Transwell assays, while tumor cell stemness was examined through sphere formation assays. Troxerutin's functional role was studied using in vivo models. Proteomic profiling of troxerutin-treated cells was performed using iTRAQ combined with LC-MS/MS to identify differentially expressed proteins (DEPs). Furthermore, luciferase reporter and ChIP assays were conducted to elucidate the underlying regulatory mechanisms. These findings demonstrate that troxerutin markedly inhibits HCC malignancy and stemness in both in vitro and in vivo models. Bioinformatics analysis indicated that the FOXO and SYK signaling pathways were predominantly enriched among the differentially expressed proteins. Mechanistically, we show that Syk dephosphorylation activates FOXO3 and facilitates its translocation into the nucleus. Moreover, we confirm that FOXO3 directly associates with the Syk promoter, thereby initiating its transcription. The present study reveals that troxerutin attenuates HCC progression by targeting the FOXO3/Syk feedback loop, inhibiting the stem-like properties of HCC cells.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of gut and oral microbiota in methamphetamine-induced multi-organ toxicity.","authors":"Jiebin Rong, Jingshen Zhuang, Jialong Xu, Xia Yue, Xuebing Chen","doi":"10.1007/s10565-026-10182-3","DOIUrl":"https://doi.org/10.1007/s10565-026-10182-3","url":null,"abstract":"<p><p>Methamphetamine (METH) is an illicit stimulant that is in widespread use worldwide. Repeated intake of METH can lead to addiction and multiple-organ damage, which has become a globalized problem. However, the mechanism of METH toxicity remains unclear. The gut and oral microbiota and their metabolites have an impact on host behavior, metabolism, nutrition, and immune response. The available research find that METH not only disrupts the intestinal microbiota, but also alters the metabolites produced by the intestinal microbiota, such as reducing the levels of short-chain fatty acids (SCFAs), indole derivatives and inosine, and increasing the levels of trimethylamine N-oxide and lipopolysaccharide (LPS). The gut microbiota and their metabolites can participate in mediating METH-induced multi-organ toxicity via the intestinal immune interface and the gut-organ axis, thereby regulating processes such as oxidative stress, inflammatory responses, and mitochondrial damage. Concurrently, therapeutic approaches targeting the affected gut microbiota (including probiotic, microbiota transplantation, SCFAs, and indole derivatives) have also been demonstrated to effectively mitigate damage caused by METH abuse. The objective of this review is to establish a link between METH and the microbiota from the gut and oral cavity, based on the available evidence, to gain insight into the potential bidirectional roles of the gut and oral microbiota in METH addiction and METH-related multi-organ toxicity, and to develop future therapeutic strategies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPSB3-mediated K48- and K63- linked ubiquitination and degradation of TUFM promote apoptosis induced by myocardial ischemia/reperfusion injury.","authors":"Yuyao Yin, Yaofeng Xie, Xiao Wang, Yuan Tan, Xiaodong Li, Yilong Pan","doi":"10.1007/s10565-026-10199-8","DOIUrl":"https://doi.org/10.1007/s10565-026-10199-8","url":null,"abstract":"<p><p>Hypoxia, caused by various factors, significantly threatens human health by damaging the heart and cardiomyocytes. Revascularization strategies can sometimes precipitate adverse clinical outcomes due to myocardial ischemia/reperfusion (I/R) injury. The primary objective of this investigation was to explore the mechanism underlying myocardial I/R injury to identify novel alleviating strategies. CRISPR/Cas9 technology was used for high-throughput screening of hypoxia/reoxygenation (H/R)-tolerant genes; afterward, the genes were intersected with differentially expressed genes in the GSE61592 dataset. Subsequent validation identified SPRY domain-containing SOCS box protein 3 (SPSB3) as a critical gene that confers resistance to H/R injury. Increased apoptosis and worse heart function were observed in mouse and cardiomyocyte models of myocardial I/R injury. These pathological alterations coincided with a marked elevation in SPSB3 expression. Furthermore, SPSB3 inhibition substantially attenuated the myocardial I/R injury-induced increase in cardiomyocyte apoptosis, decrease in cardiac function, and mitochondrial dysfunction. To identify SPSB3 substrates, we combined the results from mass spectrometry, ubiquitin-modified proteomics, and the MitoCarta3.0 database (cardiac mitochondrial proteins), yielding six candidate molecules. Co-immunoprecipitation and western blot analyses indicated that SPSB3 may bind to Tu translation elongation factor, mitochondrial (TUFM). In SPSB3-knockdown cardiomyocytes, additional TUFM knockdown partially reversed the protective effect of SPSB3 knockdown alone. Additionally, MG132 and Cycloheximide treatment effectively inhibited TUFM degradation. Further amino acid site mutagenesis and other analyses revealed that SPSB3 inhibition prevents K48- and K63-linked ubiquitination at the K259 residue of TUFM and TUFM degradation, providing a promising therapeutic avenue for mitigating myocardial I/R injury.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subthalamic CaMKIIα-expressing neurons facilitate recovery from propofol anesthesia via the STN-ventral pallidum pathway.","authors":"Shangqin Bai, Yiqiu Chen, Yu Li, Xiao Liu, Yanyan Ba, Qingbin Chen, Xiangqing Song, Haisheng Zhang, Xiaochun Lai, Lin Xue, Pei Sun, He Zhu, Jingyu Xiao, Wen Li, Xuejun Wang","doi":"10.1007/s10565-026-10195-y","DOIUrl":"https://doi.org/10.1007/s10565-026-10195-y","url":null,"abstract":"<p><p>Propofol is extensively used in clinical anesthesia, yet its mechanisms of action remain incompletely understood. CaMKIIα-expressing neurons in the subthalamic nucleus (STN) have been associated with arousal-related pain perception and impulse regulation, but their role in propofol anesthesia remains unclear. In this study, c-Fos immunohistochemistry, live calcium-signal recording by fiber photometry, electroencephalography (EEG), and electromyography (EMG) were employed to assess the activity of STN CaMKIIα-expressing neurons during propofol anesthesia. It was observed that the activity of STN CaMKIIα-expressing neurons was markedly reduced under propofol anesthesia. Both optogenetic and chemogenetic activation of this population promoted cortical arousal and shortened recovery time without affecting anesthetic induction. Through anterograde and retrograde tracing approaches, a direct projection from the STN to the ventral pallidum (VP) was identified. Optogenetic stimulation of STN CaMKIIα-expressing axon terminals within the VP modified EEG spectral power during maintenance and emergence and enhanced emergence from propofol anesthesia. Collectively, these findings indicate that STN CaMKIIα-expressing neurons play an important role in promoting behavioral emergence from propofol anesthesia, at least partially through the STN-VP circuit. This study provides circuit-level evidence that improves mechanistic insight into emergence from general anesthesia and identifies the STN-VP pathway as a potential target for modulating anesthetic recovery.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14 modulates the autophagy-pyroptosis pathway in fibroblasts by modifying BECN1 through m⁶A methylation to promote wound healing in DFUs and SYD treatment.","authors":"Zhaowei Wang, Zongqiang Wei, Qinyao Yu, Linru Wang, Kai Liu, Hongjie Wang, Qiang Li","doi":"10.1007/s10565-026-10196-x","DOIUrl":"https://doi.org/10.1007/s10565-026-10196-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) are prevalent complication in diabetes. METTL14 serves as a key regulator of both autophagy and pyroptosis, both essential for the healing of DFUs. Simiao Yong'an Decoction (SYD) has demonstrated potential in promoting skin wound healing. This study investigates how METTL14 functions as a main regulator in DFU wound healing during SYD treatment and explores the underlying mechanisms.</p><p><strong>Methods: </strong>Both qPCR and western blot assays were performed to determine METTL14 and BECN1 expression. DFU rat models and fibroblasts stimulated with high glucose (HG) were used to evaluate the role of METTL14 in autophagy, pyroptosis, pro-angiogenic ability, and wound healing through both loss- and gain-of-function assays. The association between METTL14 and BECN1 was examined via MeRIP and RNA stability assays. Futhermore, the therapeutic effects of SYD on DFUs were assessed.</p><p><strong>Results: </strong>Exposure to HG reduced METTL14 levels in fibroblasts, resulting in reduced cell viability and migration, lowered autophagy, and increased pyroptosis. Increasing METTL14 expression reversed these cellular impairments and enhanced angiogenesis driven by fibroblasts. Mechanistically, METTL14 stabilized BECN1 mRNA via m⁶A modification. In a rodent DFU model, overexpression of METTL14 accelerated wound healing, improved angiogenesis, and regulated autophagy and pyroptosis; these beneficial effects were partially reversed when BECN1 was knocked down. Furthermore, treatment with SYD increased METTL14 expression, promoted wound closure, angiogenesis, and autophagy, while reducing pyroptosis; these positive outcomes were significantly reduced when METTL14 was knocked down.</p><p><strong>Conclusions: </strong>METTL14-mediated m⁶A modification of BECN1 influences autophagy, pyroptosis, and angiogenesis to enhance wound healing in DFUs. METTL14 serves as a key regulator in SYD-mediated wound repair, offering a novel therapeutic strategy for treating DFUs.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCF12-mediated transcriptional activation of CCDC34 is involved in the positive feedback of tumor-associated macrophages and EMT to promote LUSC.","authors":"Jieli Yu, Qinyuan Zhan","doi":"10.1007/s10565-026-10200-4","DOIUrl":"https://doi.org/10.1007/s10565-026-10200-4","url":null,"abstract":"<p><p>The positive feedback loop between epithelial-mesenchymal transition (EMT) and M2-like tumor-associated macrophages (TAM-M2) contributes to tumor growth and metastasis. This research aims to investigate the regulatory mechanism of CCDC34 in the maintenance of this loop in lung squamous cell carcinoma (LUSC). Lentiviral vectors were used to knock down CCDC34, and the impact of CCDC34 knockdown on metastasis-like behaviors of LUSC cells was analyzed. LUSC cell-conditioned medium was used to analyze the influence of CCDC34 knockdown in LUSC on the M2 polarization of TAM and to verify the positive feedback loop of EMT and TAM-M2 polarization. CCDC34 was upregulated in LUSC and was related to poor patient prognosis. Knockdown of CCDC34 inhibited EMT in LUSC, decreased M2 polarization of TAM, impaired the positive feedback loop between EMT and TAM-M2 polarization, and suppressed metastasis of mouse LLC cells. TCF12 bound to the CCDC34 promoter to induce its transcription. Overexpression of CCDC34 overturned the blockade of EMT and TAM-M2 polarization by knockdown of TCF12 and promoted metastasis. Consequently, this study elucidates the essential roles of CCDC34 in the positive feedback loop between EMT and TAM-M2 in LUSC, thereby substantiating its potential as a prognostic marker.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNAJB4/HLJ1 protects against acetaminophen-induced liver injury by attenuating ER stress via HSP70.","authors":"Chih-Yun Lu, Tsung-Hsuan Hsieh, Min-Hui Chien, Wei-Lun Hsu, Wei-Jia Luo, Jung-Hsuan Chang, Chia-I Lee, Yi-Chun Chen, Cheng-Hao Fang, Ching-Hua Kuo, Sung-Liang Yu, Kang-Yi Su","doi":"10.1007/s10565-026-10198-9","DOIUrl":"https://doi.org/10.1007/s10565-026-10198-9","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) remains a leading cause of acute liver failure; however, current clinical strategies lack reliable biomarkers, predictors of susceptibility, and effective therapeutic interventions. Among these etiologies, acetaminophen (APAP) overdose is the most common cause of DILI worldwide. Heat shock proteins (HSPs), particularly members of the HSP40 family, are central regulators of cellular stress responses, yet the specific role of DNAJB4/HLJ1 in APAP-induced hepatotoxicity remains poorly defined. To address this gap, we employed DNAJB4/HLJ1-deficient mice (Dnajb4^-/-) to investigate the function of DNAJB4/HLJ1 in APAP-induced liver injury. Following APAP administration (> 400 mg/kg), Dnajb4^-/-exhibited exacerbated hepatic necrosis, elevated liver enzymes, and enhanced c-jun/JNK activation compared with Dnajb4^+/+ controls. Metabolic profiling revealed altered APAP metabolism, with reduced detoxification products and excessive oxidative metabolites, and pronounced glutathione (GSH) depletion. Transcriptomic analysis implicated DNAJB4/HLJ1 in metabolism, protein folding, and endoplasmic reticulum (ER) stress via interaction with HSP70. Consistently, ATF6, XBP1, and CHOP expression confirmed aggravated ER stress in Dnajb4^-/- livers. AlphaFold-Multimer modeling and co-immunoprecipitation validated physical interaction between DNAJB4/HLJ1 and HSP70. Restoration of DNAJB4/HLJ1 expression attenuated ER stress, c-jun/JNK activation, and liver injury, while pharmacological inhibition of ER stress confirmed its mechanistic involvement. Collectively, these findings identify DNAJB4/HLJ1 as a previously unrecognized regulator of stress signaling in APAP-induced hepatotoxicity. By modulating ER stress within the integrated cellular stress network, DNAJB4/HLJ1 limits injury progression and promotes hepatocellular resilience, highlighting its potential as a novel therapeutic target for preventing or mitigating DILI.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: BMSC‑derived extracellular vesicles affect gluconeogenesis and lipogenesis by releasing 5'‑tRF‑GlyCCC to improve MAFLD insulin sensitivity.","authors":"Chenyun Yang, Huiling Chen, Xiaojing Huang, Yanyan Li, Song Wen, Ligang Zhou, Xinlu Yuan","doi":"10.1007/s10565-026-10187-y","DOIUrl":"https://doi.org/10.1007/s10565-026-10187-y","url":null,"abstract":"","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"42 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-145-5p from BMSCs alleviates AKI-induced renal fibrosis via KLHL12/KHSRP-mediated m6A-dependent repression of FLI-1.","authors":"Fanzhou Zeng, Wei Gou, Xuezi Fu, Lingling Ding, Qing Shao, Changhao Zhu, Yuting Liu, Jin Cheng, Bo Yang, Nanmei Liu","doi":"10.1007/s10565-026-10191-2","DOIUrl":"https://doi.org/10.1007/s10565-026-10191-2","url":null,"abstract":"<p><p>Pericyte to myofibroblast transformation is a key driver of renal fibrosis following acute kidney injury (AKI). Exosomes, miRNAs, and bone mesenchymal stem cells (BMSCs) are important in alleviating AKI renal fibrosis. We proposed to explore the role of engineering exosomes rich in miR-145-5p and correlated with KLHL12/KHSRP in AKI-induced pericytes-mediated fibrosis in the present study. Rat perirenal cells were isolated and cultured. Engineering exosomes rich in miR-145-5p derived from BMSCs were obtained through cell transfection technology. AKI rat model and Hypoxia/Reoxygenation (HR) induced perirenal cells injury model were established. Dual luciferase reporter gene, MeRIP, and Co-immunoprecipitation were performed to validate miR-145-5p targeting KLHL12 and its downstream molecules including KHSRP and FLI-1. Renal function, apoptosis and pyroptosis, fibrosis-related proteins were detected through biochemistry, immunohistochemistry, immunofluorescence, and transmission electron microscopy to explore the functional role of the miR-145-5p/ KLHL12/KHSRP/FLI-1 axis in cellular and animal models. According to our findings, pericyte-myoblast transformation contributed to AKI-induced fibrosis in vivo and HR-induced fibrosis along with apoptosis and pyroptosis in vitro. MiR-145-5p down-regulated KLHL12 expression by targeting its 3'UTR to improve perirenal cells-mediated fibrosis. KLHL12 might downregulate KHSRP to increase FLI-1 expression by promoting FLI-1 mRNA stability in AKI-induced fibrosis mediated by perirenal cells. These findings indicate that miR-145-5p enriched in BMSC derived engineered exosomes may suppress KLHL12 expression to up-regulate KHSRP and then down-regulate FLI-1 by m6A to attenuate perirenal cells-mediated fibrosis.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}