APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2026
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IF 3.5
Li Yuejin,Ouyang Yiming,Zhu Yu,Hou Dezhi,Li Xing,Guo Xiaodong,Sheng Ping,Wu Hailong,Liao Yingzhong,Gong Kunmei,Li Linhai
Natural killer (NK) cells play a crucial role in combating gastric cancer (GC). However, they undergo ferroptosis in the tumor microenvironment of GC, which weakens their antitumor effects. Exosomal circRNA influences GC progression. Previous studies have reported the cancer-promoting role of circPDSS1 in GC, but whether it is involved in NK cell ferroptosis remains unclear. This study aimed to investigate the role of GC cell-derived exosomal circPDSS1 in NK cell ferroptosis. A noncontact coculture system of GC cells (HGC-27, AGS, and MKN-45 cells) and human NK-92 cells was established, and humanized mouse and cell-derived xenograft (CDX) tumor models were constructed for joint investigation. Cell death and viability were assessed via flow cytometry, LDH release assays and CCK-8 assays; circPDSS1 stability was determined by agarose gel electrophoresis and actinomycin D treatment; ferroptosis was determined by measuring lipid ROS, MDA, and Fe 2+ levels; and key molecular interactions were determined by performing dual-luciferase reporter assays and RIP and RNA pull-down experiments. CD56 and CD16 expression was reduced in clinical tumor tissues. In vitro experiments revealed that the proportion of 7-AAD + NK-92 cells cocultured with GC cells was significantly increased, accompanied by increased cell mortality and decreased IFN-γ and TNF-α secretion. Further studies revealed that circPDSS1 expression was abnormally elevated in GC tissues and cells and was particularly enriched in MKN-45 cell-derived exosomes (Exos). Knockdown of circPDSS1 alleviated MKN-45-Exo-induced cell damage; reduced lipid ROS, MDA, and Fe 2+ levels in NK-92 cells; and delayed tumor progression. Furthermore, a ferroptosis inhibitor suppressed circPDSS1 overexpression-induced cell death. Mechanistically, circPDSS1 sponged miR-142-3p to upregulate ACSL4 expression, promoting NK cell ferroptosis. Exosomal circPDSS1 derived from GC cells contributes to NK cell ferroptosis by sponging miR-142-3p to increase ACSL4 expression and exacerbate GC.
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MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2026
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IF 3.4
Yikai Lian,Jiahao Chen,Teng Zhang,Wenjing Zhang,Shaomin Huang,Mengjie Yang,Qionghua Chen,Weidong Zhou
Exosomal miR-143-5p is significantly upregulated in PCOS follicular fluid. • miR-143-5p promotes granulosa cell proliferation by directly targeting RASAL2. • Exosomal miR-143-5p serves as a novel diagnostic biomarker for PCOS. • Inhibition of miR-143-5p alleviates PCOS phenotypes in a letrozole-induced rat model. Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age, in which abnormal follicular development is a major contributor to ovulatory dysfunction and infertility. Studies have shown that granulosa cell dysfunction underlies this aberrant follicular development. Within the follicular microenvironment, exosomes serve as crucial mediators of intercellular communication. Notably, exosomal non-coding RNAs (ncRNAs) are dysregulated in PCOS and have been implicated in its pathogenesis. Nevertheless, the precise mechanisms by which these exosomal ncRNAs influence abnormal follicular development in PCOS remain to be elucidated. Methods A total of 40 PCOS patients and 45 non-PCOS controls undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment were included in this study. Exosomes and mural granulosa cells (mGCs) of those patients were isolated from follicular fluid. Cumulus granulosa cells (cGCs) were separated from the cumulus-oocyte complexes (COCs). High-throughput miRNA sequencing were performed to analyze the expression profile of miRNAs in follicular fluid exosomes from 3 PCOS patients and 3 controls, and an additional 37 PCOS and 42 control samples were used for validation. The diagnostic potential of exosomal miR-143-5p for PCOS was evaluated using receiver operating characteristic (ROC) curve analysis, and its correlation with clinical parameters was examined. Quantitative real-time PCR was used to confirm miR-143-5p expression in exosomes and granulosa cells. Functional assays in primary mural GCs (mGCs) and KGN cells investigated the effects of exosomal miR-143-5p on granulosa cell proliferation. Bioinformatic analysis combined with dual-luciferase reporter assays were performed to validate the target gene of miR-143-5p. In vivo, a letrozole-induced PCOS rat model was established to investigate the role of miR-143-5p in the pathogenesis of the disease. Results In this study, we identified exosomal miR-143-5p as significantly upregulated in follicular fluid from PCOS patients, in which it correlated with serum AMH levels and demonstrated strong diagnostic potential. Functional experiments in primary mGCs and KGN cells revealed that miR-143-5p promotes GC proliferation. Mechanistically, RASAL2 was identified and validated as a direct target of miR-143-5p. Exosomes derived from miR-143-5p-overexpressing cells enhanced recipient GC proliferation, confirming the role of exosomal mediation. In a letrozole-induced PCOS rat model, inhibition of miR-143-5p increased RASAL2 expression and ameliorated key pathological features, including ovarian weight, cystic follicle formation, and hormonal imbalances. Conclusions These findings reveal a novel exosomal miR-143-5p/RASAL2 pathway driving GC proliferation and ovarian dysfunction in PCOS, highlighting its potential as both a diagnostic biomarker and therapeutic target.
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Journal of Diabetes and Metabolic Disorders
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2026
·Vol. 25
·期 1
·142
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IF 2.1
Zhang Li,Zhang Chuanqi,Liu Yueyan,Zhang Chenchen
Background Atherosclerosis (AS) remains a major cause of cardiovascular morbidity and mortality worldwide. and Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype is a critical event in atherosclerotic lesion development. Although miR-148b has been implicated in the regulation of VSMC phenotypic switching, its functional role and underlying mechanism in AS-associated VSMC phenotypic switching remain incompletely understood. Methods An in vitro AS-related VSMC model was established by treating T/G HA-VSMCs with oxidized low-density lipoprotein (ox-LDL). Cell proliferation and migration were assessed using CCK-8, EdU incorporation, and Transwell assays. RNA and protein expression levels were determined by qRT-PCR and western blotting, respectively. The targeted relationship between miR-148b and KLF4 was examined using dual-luciferase reporter and RNA immunoprecipitation assays. KLF4 protein stability and ubiquitination were assessed using cycloheximide chase, MG132 treatment, and immunoprecipitation followed by western blotting. Results miR-148b expression was significantly reduced in ox-LDL-treated VSMCs. Overexpression of miR-148b suppressed ox-LDL-induced VSMC proliferation and migration, and restored the expression of contractile phenotype markers, including SM22α and α-SMA. Mechanistically, KLF4 was identified as a downstream target of miR-148b. miR-148b reduced KLF4 expression through 3′-UTR-mediated repression and was associated with enhanced ubiquitination-dependent KLF4 protein degradation. Rescue experiments showed that KLF4 overexpression partially reversed the inhibitory effects of miR-148b on VSMC proliferation, migration, and phenotypic switching. Conclusion miR-148b attenuates ox-LDL-induced VSMC phenotypic switching, at least in part, by downregulating KLF4. These findings suggest that the miR-148b/KLF4 axis may represent a potential regulatory mechanism in AS-associated vascular remodeling .
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Lei Jin,Cao Kun,Chen Huimin,Hou Jinhuan,Li Taiqin,Zhang Ya,Chen Chengxin,Ma Huaxing,Jin Jiliang,Qian Junxue,Li Zhi,Zhang Tian,Zuo Shi,Linghu Kegang,Li Haiyang
Chronic liver fibrosis remains a major healthcare burden with no approved pharmacotherapies currently available that directly target the fibrotic process. Although apoptotic vesicles (apoVs) derived from human umbilical cord mesenchymal stem cells (hUMSCs) hold great therapeutic potential for tissue repair, their mechanisms in alleviating liver fibrosis and their feasibility as siRNA carriers remain unclear. Here, we demonstrate that systemically administered apoVs exhibit robust liver tropism, efficiently delivering miR-6869-5p to both hepatic stellate cells (HSCs) and macrophages. Mechanistically, miR-6869–5p directly targets fibroblast growth factor 1 (FGF1) to suppress the PI3K/AKT/mTOR signaling pathway, thereby inhibiting HSC activation and reducing collagen deposition. Simultaneously, it targets high-mobility group box 1 (HMGB1) to attenuate NF-κB activity and establish an antifibrotic microenvironment through HSC-macrophage crosstalk. In clinical cohorts ( n = 100), serum miR-6869 − 5p levels were inversely correlated with fibrosis indices. Leveraging these unique properties, we engineered apoVs loaded with antifibrotic TANGO1 siRNA (si-apoVs), which blocks collagen secretion; this achieves enhanced antifibrotic efficacy in CCl₄-induced liver fibrosis models while mitigating the pro-inflammatory side effects associated with free siRNA. This study identifies hUMSC-derived apoVs as a liver-targeted, dual-action therapeutic platform, and si-apoVs represent a potent, translation-ready strategy for the treatment of liver fibrosis. Graphical abstract The alternative text for this image may have been generated using AI.
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Stem Cell Research & Therapy
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2026
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IF 7.8
Li Xiao-huan,Lian Fu-wei,Lv Feng,Luo Xiao-Ling,Hu Bang-li,Zhang Li-tu,Ning Shu-fang
Background Mesenchymal stem cells (MSCs)-derived exosomes present great potential as nanocarriers for targeted drug delivery. Moreover, the therapeutic efficacy of exosomes can be substantially enhanced through functional modifications and the incorporation of bioactive molecules. Methods In this study, the MSCs were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. The culture supernatants were collected for isolating exosomes. The characteristics and yields of exosomes from 2D and 3D cultures were detected by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and modified with iRGD peptide were formed into a new engineered exosome, designated as iRGD-Exo-miR-99b-5p. The effects of these engineered exosomes on the progression of colorectal cancer (CRC) were assessed through a series of in vivo and in vitro experiments. Results The 3D-cultured MSCs exhibited a higher yield of exosomes and enhanced uptake by CRC cells. Further in vitro experiments demonstrated that 3D-exosomes loaded with miR-99b-5p effectively inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells. Results from a xenograft tumor model indicate that iRGD-modified exosomes were significantly enriched at tumor sites. Furthermore, exosomes modified with iRGD and loaded with miR-99b-5p were employed for CRC treatment, resulting in substantial tumor growth inhibition and enhanced the chemotherapy efficacy of 5-fluorouracil (5-FU) in vivo, without inducing notable toxicity or side effects. Mechanistically, exosome-mediated delivery of miR-99b-5p downregulated FGFR3 expression, thereby inhibiting the activation of the PI3K/AKt signaling pathway and promoting ferroptosis, ultimately attenuating CRC progression. Conclusions Collectively, iRGD-modified 3D exosomes loaded with miR-99b-5p were able to specifically target tumor sites, thereby significantly suppressing CRC growth through the induction of ferroptosis via regulating the FGFR3/PI3K/AKt signaling pathway. These findings suggest that functional engineering and bioactive loading of 3D-exosomes derived from MSCs represent a promising strategy for targeted cancer therapy. Graphical
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Hong Yu,Muyan Kong,Jinyi Chen,Jiyao Liu,Keyao Shan,Guiyu Zhang,Ruidi Jiang,Yinli Zheng,Qiulu Chen,Rong Zhang,Zhongqiu Liu,Jinjun Wu
Colorectal cancer (CRC), one of the primary causes of gastrointestinal malignancy-related mortality worldwide, encounters significant therapeutic challenges due to multidrug resistance. Multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2, plays a crucial role in the development of drug resistance during clinical CRC treatment. This study elucidates a novel mechanism by which formononetin (FMNT), a bioactive isoflavone commonly found in food and medicinal-related plants, suppresses CRC via microRNA-490-3p (miR-490-3p)-mediated regulation of ABCC2 and synergizes with 5-fluorouracil (5-FU). HCT116 and SW480 cell lines as well as AOM/DSS-induced CRC models in wild-type and Mrp2 -/- mice were employed. The results demonstrated that FMNT markedly suppresses CRC proliferation in vitro and tumorigenesis in vivo . Transcriptomic profiling identified ABCC2 as the top target associated with FMNT’s efficacy. This finding was validated in clinical specimens, which revealed significant upregulation of MRP2 in human CRC tissues. FMNT markedly downregulated the MRP2 expression. Genetic ablation experiments further confirmed enhanced FMNT sensitivity in Mrp2 -/- mice and MRP2 silencing CRC cells. Mechanistically, FMNT upregulated tumor-suppressive miR-490-3p, which directly targets the ABCC2 3′UTR, thereby establishing a regulatory axis corroborated by gain/loss-of-function experiments. Notably, overexpression of miR-490-3p augmented FMNT’s antitumor effects, whereas inhibition of miR-490-3p diminished its efficacy. Therapeutic combination index analysis indicated robust synergy between FMNT and 5-FU, with combination therapy achieving superior tumor growth inhibition compared to monotherapies. Collectively, our findings uncover a novel miR-490-3p/ABCC2 regulatory mechanism underlying FMNT’s antitumor activity and highlight its potential for chemosensitization through ABCC2 inhibition, providing a strong rationale for flavonoid-based adjuvant therapy in CRC management.
研究领域:
肿瘤学
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分子生物学
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药理学
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癌症研究
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生物信息学
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Wenjia Guo,Haifeng Huang,Hong Wang,Xiaodan Tan,Yujun Tu,Chao Gu,Pu Xiang,Lin Chen,Zhe Peng,Yang Yang,Dongzhi Ran,Yin Luo,Junqing Yang
The objective of this study was to explore the effects and underlying mechanisms of miR-690 on hepatic steatosis in db/db mice. Our findings revealed that miR-690 was downregulated in the liver of db/db mice and high-glucose (HG)-treated NCTC1469 cells. In vivo, miR-690 overexpression alleviated hyperglycemia, hyperlipidemia, and hyperinsulinemia, improved liver function, and mitigated steatosis and pathological damage. In vitro , miR-690 enhanced cell viability and glucose uptake while reducing lipid deposition. Mechanistically, bioinformatics analysis identified 15-LOX and NF-KappaB P65 as potential miR-690 targets, with their expression levels inversely correlated with miR-690. Furthermore, treatment with miR-690 agomir downregulated 15-LOX and NF-KappaB P65, although dual-luciferase reporter assays confirmed that 15-LOX is indirectly targeted by miR-690. Additionally, miR-690 agomir increased LC3BII/I and Beclin1 levels while decreased P62 and p-mTOR (Ser2448)/mTOR and induced autophagosome formation. Moreover, overexpression of 15-LOX or NF-KappaB P65 reversed the protective effects of miR-690 on autophagy. Collectively, these results suggest that miR-690 exerts hepatoprotective effects against diabetic hepatic steatosis by activating autophagy via modulating 15-LOX and NF-KappaB P65, providing experimental evidence for its potential use in the treatment of hepatic steatosis in diabetes, and new insight into diabetes drug development for targeting miR-690.
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BMC GASTROENTEROLOGY
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2026
·Vol. 26
·期 1
·120
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IF 3.2
Teng Xiao,Sheng Shanfeng,Pan Mingyuan,Li Yuyang,Li Zheng
Background Severe acute pancreatitis (SAP) is a critical gastrointestinal disorder associated with high mortality. Dysregulated ferroptosis, an iron-dependent form of cell death, is recognized as a pivotal mechanism driving SAP progression. Although Homoplantaginin (Homo) exhibits notable anti-inflammatory and antioxidant properties, its specific role in modulating ferroptosis during SAP remains unclear. Objective To investigate whether Homo alleviates SAP by inhibiting ferroptosis via the circDNMT3B/miR-20b-5p/SLC7A11 axis. Methods C57BL/6 mice ( n = 10 per group) were randomly allocated into nine groups, including normal control, SAP model, and various intervention groups involving Homo treatment, circDNMT3B knockdown, and miR-20b-5p inhibition. SAP was induced via caerulein and LPS injections. Assessments included histopathological evaluation, serum analysis (amylase, cytokines IL-1β, IL-6, IL-18), measurement of ferroptosis markers (MDA, GSH, tissue iron), Western blotting for ferroptosis-related proteins (ACSL4, COX-2, SLC7A11, GPX4), and qRT-PCR for gene expression. The targeting relationship between miR-20b-5p and SLC7A11 was validated by dual-luciferase reporter assay. Results SAP mice demonstrated severe pancreatic injury and hallmarks of ferroptosis, including elevated inflammation, iron accumulation, increased ACSL4/COX-2 expression, and upregulation of miR-20b-5p, alongside suppressed SLC7A11 and GPX4. Homo treatment significantly mitigated pancreatic damage and reversed these ferroptosis-related changes. CircDNMT3B knockdown exacerbated SAP severity and attenuated the protective effect of Homo, indicating its dependence on circDNMT3B. Furthermore, the detrimental effects of circDNMT3B knockdown were partially rescued by concurrent inhibition of miR-20b-5p, suggesting that miR-20b-5p acts downstream of circDNMT3B within the protective pathway mediated by Homo. The dual-luciferase assay confirmed miR-20b-5p directly targets SLC7A11. Conclusion Our study demonstrates that Homo protects against SAP primarily by suppressing ferroptosis. Mechanistically, Homo upregulates circDNMT3B, which sequesters miR-20b-5p, thereby relieving its repression of SLC7A11, which in turn supports the GPX4-mediated antioxidant defense. These findings elucidate a novel molecular pathway in SAP-associated ferroptosis and highlight the circDNMT3B/miR-20b-5p/SLC7A11 axis as a promising therapeutic target.
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BIOMARKERS
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2026
·
IF 1.9
Yang Jiang,Xiaosheng Jin
Background PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.Methods Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.Results Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.Conclusion Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.
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International Journal of Stem Cells
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2021
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IF 2.5
Qiong Li,Lei Huang
Background and Objectives MiR-148a-3p has been reported to regulate the differentiation of marrow stromal cell osteoblast. In this study, whether miR-148a-3p regulated the odontoblastic differentiation of human dental pulp stem cells (hDPSCs) or not was explored. Methods and Results The hDPSCs were isolated and identified via flow cytometry. Targets of miR-148a-3p were identified via bioinformatics and dual-luciferase reporter assay. After the cell was cultured in the odontogenic differentiation medium or infected, cell viability, invasion, and odontoblastic differentiation were detected via MTT, transwell, and Alizarin Red S staining, respectively. The miR-148a-3p, Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions were determined by RT-qPCR and Western blot. The hDPSCs odontoblastic differentiation downregulated the miR-148a-3p expression and upregulated Wnt1 expression. Wnt1 was determined as the target for miR-148a-3p. MiR-148a-3p mimic and siWnt1 suppressed the cell viability, invasion, and odontoblastic differentiation of hDPSCs and inhibited the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. In contrast, miR-148a-3p inhibitor and overexpressed Wnt1 promoted the cell viability, invasion, and odontoblastic differentiation of hDPSCs, and upregulated the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. Also, miR-148a-3p mimic and inhibitor reversed the effects of Wnt1 overexpression and siWnt1. Conclusions MiR-148a-3p modulated the invasion and odontoblastic differentiation of hDPSCs through the Wnt1/β-catenin pathway.
研究领域:
牙科研究
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干细胞生物学
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分子生物学
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细胞分化
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JOURNAL OF CELLULAR PHYSIOLOGY
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2023
·Vol. 238
·期 6
·1256-1274
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IF 5.6
Zhe Li,Tong Xu,Xue Fan,Kai Chen,Chunyan Wan,Xiang Li,Hang Yin,Shu Li
Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l -cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.
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JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Rui Zhang,Jingyao Guo,Yupeng Wang,Rundong Sun,Guangzhu Dong,Xinru Wang,Guizhen Du
The increased usage of bisphenol S (BPS) results in wide distribution in pregnant women. In this study, pregnant mice were given multiple-dose BPS during gestation. Results showed that prenatal BPS exposure (50 μg/kg/day) induced increased weight gain, dyslipidemia, higher liver triglyceride (TG), adipocyte hypertrophy, and hepatic lipid deposition in male offspring . Exosomes play important roles in regulating lipid metabolism . Here, serum exosomes and adipose miRNA sequencing of male offspring indicated a remarkable decrease in miR-29a-3p expression. To clarify whether adipocyte-derived exosomes mediate hepatic lipid deposition, exosomes were extracted from BPS-treated adipocytes and co-cultured with hepatocytes. These exosomes could be taken up by hepatocytes and promoted lipid deposition, and notably, exosomal miR-29a-3p was downregulated. Furthermore, miR-29a-3p knockdown in adipocyte-derived exosomes promoted hepatocyte lipid deposition, whereas overexpression led to the opposite effect. Also, the role of miR-29a-3p was demonstrated in hepatocytes by overexpressing or knocking it down. Subsequent studies have shown that miR-29a-3p can promote lipid deposition by directly targeting Col4a1 . Taken together, prenatal BPS exposure could lead to lower miR-29a-3p yield in adipocyte-derived exosomes and decrease miR-29a-3p content transported to hepatocytes, which further negatively regulate Col4a1 and promote hepatic lipid deposition. Our findings provided clues to maternal environmental exposure-induced liver metabolic diseases.
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