Journal of Cellular Physiology最新文献

{"title":"Mitochondrial metabolism: A moving target in hepatocellular carcinoma therapy","authors":"Monika Komza,&nbsp;Jerry Edward Chipuk","doi":"10.1002/jcp.31441","DOIUrl":"10.1002/jcp.31441","url":null,"abstract":"<p>Mitochondria are pivotal contributors to cancer mechanisms due to their homeostatic and pathological roles in cellular bioenergetics, biosynthesis, metabolism, signaling, and survival. During transformation and tumor initiation, mitochondrial function is often disrupted by oncogenic mutations, leading to a metabolic profile distinct from precursor cells. In this review, we focus on hepatocellular carcinoma, a cancer arising from metabolically robust and nutrient rich hepatocytes, and discuss the mechanistic impact of altered metabolism in this setting. We provide distinctions between normal mitochondrial activity versus disease-related function which yielded therapeutic opportunities, along with highlighting recent preclinical and clinical efforts focused on targeting mitochondrial metabolism. Finally, several novel strategies for exploiting mitochondrial programs to eliminate hepatocellular carcinoma cells in metabolism-specific contexts are presented to integrate these concepts and gain foresight into the future of mitochondria-focused therapeutics.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interactome of cystic fibrosis transmembrane conductance regulator and its role in male fertility: A critical review","authors":"João C. Ribeiro,&nbsp;Bernardo C. Rodrigues,&nbsp;Raquel L. Bernardino,&nbsp;Marco G. Alves,&nbsp;Pedro F. Oliveira","doi":"10.1002/jcp.31422","DOIUrl":"10.1002/jcp.31422","url":null,"abstract":"<p>The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic adenosine monophosphate (cAMP)-regulated chloride and bicarbonate ion channel found in many human cells. Its unique biochemical characteristics and role as a member of the adenosine triphosphate (ATP)-binding cassette transporters superfamily are pivotal for the transport of several substrates across cellular membranes. CFTR is known to interact, physically and functionally, with several other cellular proteins. Hence, its properties are essential for moving various substances across cell membranes and ensuring correct cell functioning. Genetic mutations or environmental factors may disrupt CFTR's function resulting in different possible phenotypes due to gene variations that affect not only CFTR's function, localization, and processing within cells, but also those of its interactors. This has been reported as an underlying cause of various diseases, including cystic fibrosis. The severe clinical implications of cystic fibrosis have driven intense research into the role of CFTR in lung function but its significance to fertility, particularly in men, has been comparatively understudied. However, ongoing and more recent research into CFTR and its interacting proteins in the testis or specific testicular cells is beginning to shed light on this field. Herein, we provide a comprehensive and up-to-date overview of the CFTR, its interactome, and its crucial role in male reproduction, highlighting recent discoveries and advancements in understanding the molecular mechanisms involved. The comprehension of these complex interactions may pave the way for potential therapeutic approaches to improve fertility of men suffering from alterations in the function of CFTR.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCDC158: A novel regulator in renal proximal tubular endocytosis unveiled through exome sequencing and interactome analysis","authors":"Tjessa Bondue,&nbsp;Francesca Cervellini,&nbsp;Bart Smeets,&nbsp;Sergei V. Strelkov,&nbsp;Flore Horuz-Engels,&nbsp;Koenraad Veys,&nbsp;Rosa Vargas-Poussou,&nbsp;Maria Antonietta De Matteis,&nbsp;Leopoldo Staiano,&nbsp;Lambertus van den Heuvel,&nbsp;Elena Levtchenko","doi":"10.1002/jcp.31447","DOIUrl":"10.1002/jcp.31447","url":null,"abstract":"<p>Renal proximal tubular reabsorption of proteins and polypeptides is tightly regulated by a concerted action of the multi-ligand receptors with subsequent processing from the clathrin-coated pits to early/recycling and late endosomes and towards lysosomes. We performed whole exome-sequencing in a male patient from a consanguineous family, who presented with low- and intermediate molecular weight proteinuria, nephrocalcinosis and oligospermia. We identified a new potential player in tubular endocytosis, coiled-coil domain containing 158 (CCDC158). The variant in <i>CCDC158</i> segregated with the phenotype and was also detected in a female sibling with a similar clinical kidney phenotype. We demonstrated the expression of this protein in kidney tubules and modeled its structure <i>in silico</i>. We hypothesized that the protein played a role in the tubular endocytosis by interacting with other endocytosis regulators, and used mass spectrometry to identify potential interactors. The role of CCDC158 in receptor-mediated endocytosis was further confirmed by transferrin and GST-RAP trafficking analyses in patient-derived proximal tubular epithelial cells. Finally, as CCDC158 is known to be expressed in the testis, the presence of oligospermia in the male sibling further substantiated the pathogenic role of the detected missense variant in the observed phenotype. In this study, we provide data that demonstrate the potential role of CCDC158 in receptor-mediated endocytosis, most likely by interaction with other endocytosis-related proteins that strongly correlate with the proximal tubular dysfunction phenotype as observed in the patients. However, more studies are needed to fully unravel the molecular mechanism(s) in which CCDC158 is involved.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An inherited TBX3 alteration in a prenatal case of ulnar-mammary syndrome: Clinical assessment and functional characterization in Drosophila melanogaster","authors":"Irene Bottillo,&nbsp;Andrea D'Alessandro,&nbsp;Maria Pia Ciccone,&nbsp;Gianluca Cestra,&nbsp;Gianluca Di Giacomo,&nbsp;Evelina Silvestri,&nbsp;Marco Castori,&nbsp;Francesco Brancati,&nbsp;Andrea Lenzi,&nbsp;Alessandro Paiardini,&nbsp;Silvia Majore,&nbsp;Giovanni Cenci,&nbsp;Paola Grammatico","doi":"10.1002/jcp.31440","DOIUrl":"10.1002/jcp.31440","url":null,"abstract":"<p>Ulnar mammary syndrome (UMS) results from heterozygous variants in the <i>TBX3</i> gene and impacts limb, tooth, hair, apocrine gland, and genitalia development. The expressivity of UMS is highly variable with no established genotype–phenotype correlations. <i>TBX3</i> belongs to the <i>Tbx</i> gene family, which encodes transcription factors characterized by the presence of a T-box DNA-binding domain. We describe a fetus exhibiting severe upper limb defects and harboring the novel <i>TBX3</i>:c.400 C &gt; T (p.P134S) variant inherited from the mother who remained clinically misdiagnosed until prenatal diagnosis. Literature revision was conducted to uncover the <i>TBX3</i> clinical and mutational spectrum. Moreover, we generated a <i>Drosophila</i> humanized model for <i>TBX3</i> to study the developmental consequences of the p.P134S as well as of other variants targeting different regions of the protein.</p><p>Phenotypic analysis in flies, coupled with <i>in silico</i> modeling on the <i>TBX3</i> variants, suggested that the c.400 C &gt; T is UMS-causing and impacts TBX3 localization. Comparative analyses of the fly phenotypes caused by the expression of all variants, demonstrated that missense changes in the T-box domain affect more significantly TBX3 activity than variants outside this domain. To improve the clinicians' recognition of UMS, we estimated the frequency of the main clinical features of the disease. Core features often present pre-pubertally include defects of the ulna and/or of ulnar ray, hypoplastic nipples and/or areolas and, less frequently, genitalia anomalies in young males. These results enhance our understanding of the molecular basis and the clinical spectrum of UMS, shedding light on the functional consequences of <i>TBX3</i> variants in a developmental context.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.31440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice","authors":"Ling Jin,&nbsp;Bo Bao,&nbsp;Xiao-Ting Huang,&nbsp;Jia-Hao Tao,&nbsp;Jia-Xi Duan,&nbsp;Wen-Jin Zhong,&nbsp;Chen-Yu Zhang,&nbsp;Yu-Biao Liu,&nbsp;Hui Chen,&nbsp;Nan-Shi-Yu Yang,&nbsp;Cha-Xiang Guan,&nbsp;Yong Zhou","doi":"10.1002/jcp.31442","DOIUrl":"10.1002/jcp.31442","url":null,"abstract":"<p>The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. <i>In vitro</i>, we found a notable increase in MEOX1 expression in transforming growth factor-β1 (TGF-β1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased histone H3K9 dimethylation in synergy with DNA demethylation of Spi-1 binding site contributes to ADAMTS-5 expression in articular cartilage of osteoarthritis mice","authors":"Shuaichen Yan,&nbsp;Tongxin Lu,&nbsp;Huapu Yang,&nbsp;Liang Ma,&nbsp;Yuankai Zhang,&nbsp;Deqiang Li","doi":"10.1002/jcp.31444","DOIUrl":"10.1002/jcp.31444","url":null,"abstract":"<p>Osteoarthritis (OA) is defined by articular cartilage degeneration, synovial membrane inflammation, and abnormal bone remodeling. Recent study has discovered that OA development is linked to an aberrant epigenetic modification of OA-related genes. Our previous research showed that DNA demethylation in ADAMTS-5 promoter region had a substantial impact on ADAMTS-5 expression in the mouse OA model. This process facilitated the binding of Spi-1 to ADAMTS-5 promoter. While alterations in histone methylation have been documented during embryonic development and cancer development, there is a paucity of data on the change in OA pathogenesis. Even no data have been reported on the role of histone modifications in ADAMTS-5 activation in OA. Following our previous study on the role of DNA methylation, we aimed to examine the contribution of histone H3K9 dimethylation in ADAMTS-5 activation in OA. Additionally, we aimed to elucidate the molecular mechanisms underlying the cooperative interaction between DNA methylation and histone H3K9 dimethylation. The potential for anti-OA intervention therapy which is based on modulating histone H3K9 dimethylation is also explored. We demonstrated that a reduction in histone H3K9 dimethylation, along with DNA demethylation of the Spi-1 binding site, had a role in ADAMTS-5 activation in the articular cartilage of OA mice. Significantly, the conditional deletion of histone demethylase to be identified as lysine-specific demethylase 1 (LSD1) in articular cartilage could alleviate the degenerative features of OA mice. Our study demonstrates the direct impact of histone H3K9 dimethylation on gene expression, which in turn contributes to OA development. This research enhances our understanding of the underlying causes of OA.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maslinic acid prevented lipopolysaccharide-induced injury of IPEC-J2 cells through regulating PTEN-FAK signaling pathway","authors":"Rui Wang,&nbsp;Hao Yu,&nbsp;Aike Li,&nbsp;Ting Wang,&nbsp;Qiyuan Wang,&nbsp;Huiyu Qi,&nbsp;Chuanqi Wang,&nbsp;Jing Zhang","doi":"10.1002/jcp.31446","DOIUrl":"10.1002/jcp.31446","url":null,"abstract":"<p>Intestinal epithelial injury is one of the typical symptoms associated with intestinal inflammation and diarrhea, and the repair of the intestinal epithelium intricately linked to cell migration. Here, we test the hypothesis that maslinic acid (MA) regulates porcine intestinal epithelial cell migration by inhibiting focal adhesion kinase (FAK)/AKT signaling pathway. In this experiment, the optimal concentration of MA (0.5 μg/mL) on IPEC-J2 cell viability was selected to investigate the effect under low-dose lipopolysaccharide (LPS) (1 μg/mL) conditions. Transcriptome sequencing and polymerase chain reaction array results revealed that MA could alleviate LPS-induced the gene expressions decreasing in focal adhesion signaling pathway. From the pathway map analysis and western blot analysis results, MA alleviated the LPS-induced decrease in FAK protein expression mainly by promoting FAK protein phosphorylation, which in turn alleviated the decrease in cell migration and formation of cytoskeleton protein Vinculin and F-actin, the above results were verified by FAK phosphorylation inhibitors Defactinib. The molecular docking and immunoprecipitation further verified that MA could bind to PTEN protein and significantly inhibit its interaction with FAK protein, blocking the function of PTEN to inhibit FAK phosphorylation finally shown to promote the level of FAK phosphorylation, meanwhile LPS inhibited FAK protein expression and its binding to PKC and PTEN proteins. Our study revealed the role of MA and LPS in FAK protein, and increased understanding of MA anti-inflammatory mechanism.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trim21 mediates metabolic reprogramming in renal tubular cells via PFKP ubiquitination to alleviate renal fibrosis","authors":"Yang Wen,&nbsp;Maoqing Tian,&nbsp;Xushun Jiang,&nbsp;Ying Gong,&nbsp;Hua Gan","doi":"10.1002/jcp.31439","DOIUrl":"10.1002/jcp.31439","url":null,"abstract":"<p>Chronic kidney disease (CKD), stemming from varied nephric impairments, manifests a steadily escalating global incidence. As a progressive pathological condition, CKD is typified by an intensification in the gravity of renal interstitium fibrotic transformations. Nonetheless, the intrinsic mechanisms underpinning nephric fibrosis remain elusive. In this context, we elucidated a marked augmentation in aerobic glycolysis within proximal tubular epithelial cells (TECs) of CKD patients, alongside unilateral ureteral obstruction (UUO) and ischemia-reperfusion injury (IRI) murine models, concomitant with deficiency of Trim21. Experimental investigations, both in vivo and in vitro, revealed that Trim21 deficiency aggravates the aberrantly heightened aerobic glycolysis, thereby exacerbating fibrotic reaction progression. Concomitantly, enhancive glycolytic flux paralleled an elevation in ATP genesis and reconstitution of cytoskeletal architecture. Mechanistically, we uncovered that Trim21 modulates aerobic glycolysis in TECs via ubiquitin-facilitated degradation of phosphofructokinase platelet (PFKP), thus attenuating nephric fibrosis. Collectively, our insights posit Trim21 as a prospective therapeutic target in the amelioration of renal fibrosis.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine demethyltransferase FTO alleviates sepsis by upregulating BNIP3 to induce mitophagy","authors":"Pingping Qi,&nbsp;Wei Zhang,&nbsp;Yang Gao,&nbsp;Shengkui Chen,&nbsp;Minghe Jiang,&nbsp;Rong He,&nbsp;Wenzhong Chen,&nbsp;Xiawei Wei,&nbsp;Bingquan Hu,&nbsp;Hao Xu,&nbsp;Minsheng Wu,&nbsp;Rong Tang","doi":"10.1002/jcp.31448","DOIUrl":"10.1002/jcp.31448","url":null,"abstract":"<p>N6-methyladenosine (m6A) is known to be crucial in various biological processes, but its role in sepsis-induced circulatory and cardiac dysfunction is not well understood. Specifically, mitophagy, a specialized form of autophagy, is excessively activated during lipopolysaccharide (LPS)-induced myocardial injury. This study aimed to investigate the impact of LPS-induced endotoxemia on m6A-RNA methylation and its role in regulating mitophagy in sepsis-induced myocardial dysfunction. Our research demonstrated that FTO (fat mass and obesity-associated protein), an m6A demethylase, significantly affects abnormal m6A modification in the myocardium and cardiomyocytes following LPS treatment. In mice, cardiac dysfunction and cardiomyocyte apoptosis worsened after adeno-associated virus serotype 9 (AAV9)-mediated FTO knockdown. Further analyses to uncover the cellular mechanisms improving cardiac function showed that FTO reduced mitochondrial reactive oxygen species, restored both basal and maximal respiration, and preserved mitochondrial membrane potential. We revealed that FTO plays a critical role in activating mitophagy by targeting BNIP3. Additionally, the cardioprotective effects of AAV-FTO were significantly compromised by mdivi-1, a mitophagy inhibitor. Mechanistically, FTO interacted with BNIP3 transcripts and regulated their expression in an m6A-dependent manner. Following FTO silencing, BNIP3 transcripts with elevated m6A modification levels in their coding regions were bound by YTHDF2 (YT521-B homology m6A RNA-binding protein 2), leading to mRNA destabilization and decreased BNIP3 protein levels. These findings highlight the importance of FTO-dependent cardiac m6A methylation in regulating mitophagy and enhance our understanding of this critical interplay, which is essential for developing therapeutic strategies to protect cardiac mitochondrial function, alleviate cardiac dysfunction, and improve survival during sepsis.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KDF1 promotes ameloblast differentiation by inhibiting the IKK/IκB/NF-κB axis","authors":"Hangbo Liu,&nbsp;Miao Yu,&nbsp;Kai Sun,&nbsp;Jinglei Zheng,&nbsp;Jiayu Wang,&nbsp;Haochen Liu,&nbsp;Hailan Feng,&nbsp;Yang Liu,&nbsp;Dong Han","doi":"10.1002/jcp.31437","DOIUrl":"10.1002/jcp.31437","url":null,"abstract":"<p>Enamel protects teeth from external irritation and its formation involves sequential differentiation of ameloblasts, a dental epithelial cell. <i>Keratinocyte differentiation factor 1</i> (<i>KDF1</i>) is important in the development of epithelial tissues and organs. However, the specific role of <i>KDF1</i> in enamel formation and corresponding regulatory mechanisms are unclear. This study demonstrated that <i>KDF1</i> was persistently expressed in all stages of ameloblast differentiation, through RNAscope in situ hybridization. <i>KDF1</i> expression in the mouse ameloblast cell line LS8 was demonstrated via immunofluorescence assay. <i>KDF1</i> was knocked out in LS8 cells using the CRISPR/Cas-9 system or overexpressed in LS8 cells through lentiviral infection. In vitro ameloblast differentiation induction, quantitative reverse transcription PCR, western blot analysis, and alkaline phosphatase (ALP) assay indicated that knockout or overexpression of <i>KDF1</i> in LS8 cells decreased or increased the mRNA and protein levels of several key amelogenesis markers, as well as ALP activity. Furthermore, liquid chromatography-mass spectrometry and co-immunoprecipitation analyses revealed that KDF1 can interact with the IKK complex, thereby inhibiting the NF-κB pathway. Suppressing NF-κB activity partially recovered the decreased ameloblast differentiation in LS8 cells induced by <i>KDF1-</i>knockout. This study demonstrated that KDF1 can promote ameloblast differentiation of LS8 cells by inhibiting the IKK/IκB/NF-κB axis, and is a potential target for functional enamel regeneration.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.31437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}