CellsPub Date : 2024-10-19DOI: 10.3390/cells13201735
Claudette O Adegboro, Wenxiang Luo, Meha Kabra, Ryan M McAdams, Nathaniel W York, Ruwandi I Wijenayake, Kiana M Suchla, De-Ann M Pillers, Bikash R Pattnaik
{"title":"Transplacental Transfer of Oxytocin and Its Impact on Neonatal Cord Blood and In Vitro Retinal Cell Activity.","authors":"Claudette O Adegboro, Wenxiang Luo, Meha Kabra, Ryan M McAdams, Nathaniel W York, Ruwandi I Wijenayake, Kiana M Suchla, De-Ann M Pillers, Bikash R Pattnaik","doi":"10.3390/cells13201735","DOIUrl":"https://doi.org/10.3390/cells13201735","url":null,"abstract":"<p><p>The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23-42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood-retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495971","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":"AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling.","authors":"Takashi Nakanishi, Yu-Ichiro Koma, Shoji Miyako, Rikuya Torigoe, Hiroki Yokoo, Masaki Omori, Keitaro Yamanaka, Nobuaki Ishihara, Shuichi Tsukamoto, Takayuki Kodama, Mari Nishio, Manabu Shigeoka, Hiroshi Yokozaki, Yoshihiro Kakeji","doi":"10.3390/cells13201733","DOIUrl":"https://doi.org/10.3390/cells13201733","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of <i>AREG</i> in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495911","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}
CellsPub Date : 2024-10-19DOI: 10.3390/cells13201734
So-Hee Kim, Chan-Jin Kim, Eun-Yeong Lee, Young-Hwa Hwang, Seon-Tea Joo
{"title":"Chicken Embryo Fibroblast Viability and Trans-Differentiation Potential for Cultured Meat Production Across Passages.","authors":"So-Hee Kim, Chan-Jin Kim, Eun-Yeong Lee, Young-Hwa Hwang, Seon-Tea Joo","doi":"10.3390/cells13201734","DOIUrl":"https://doi.org/10.3390/cells13201734","url":null,"abstract":"<p><p>This study was conducted to analyze the viability of primary chicken embryo fibroblasts and the efficiency of adipogenic trans-differentiation for cultured meat production. In isolating chicken embryo fibroblasts (CEFs) from a heterogeneous cell pool containing chicken satellite cells (CSCs), over 90% of CEFs expressed CD29 and vimentin. The analysis of the proliferative capabilities of CEFs revealed no significant differences in EdU-positive cells (%), cumulative cell number, doubling time, and growth rate from passage 1 to passage 9 (<i>p</i> > 0.05). This indicates that CEFs can be isolated by 2 h of pre-plating and survive stably up to passage 9, and that primary fibroblasts can serve as a valuable cell source for the cultured meat industry. Adipogenic trans-differentiation was induced up to passage 9 of CEFs. As passages increased, lipid accumulation and adipocyte size significantly decreased (<i>p</i> < 0.05). The reduced differentiation rate of primary CEFs with increasing passages poses a major challenge to the cost and efficiency of cultured meat production. Thus, effective cell management and the maintenance of cellular characteristics for a long time are crucial for ensuring stable and efficient cultured fat production in the cultured meat industry.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495930","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201724
Elisa Gozlan, Yarden Lewit-Cohen, Dan Frenkel
{"title":"Sex Differences in Astrocyte Activity.","authors":"Elisa Gozlan, Yarden Lewit-Cohen, Dan Frenkel","doi":"10.3390/cells13201724","DOIUrl":"https://doi.org/10.3390/cells13201724","url":null,"abstract":"<p><p>Astrocytes are essential for maintaining brain homeostasis. Alterations in their activity have been associated with various brain pathologies. Sex differences were reported to affect astrocyte development and activity, and even susceptibility to different neurodegenerative diseases. This review aims to summarize the current knowledge on the effects of sex on astrocyte activity in health and disease.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495947","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201731
Jared M Campbell, Saabah B Mahbub, Ayad G Anwer, Abbas Habibalahi, Stan Gronthos, Sharon Paton, Shane T Grey, Lindsay E Wu, Robert B Gilchrist, Ewa M Goldys
{"title":"Multispectral Imaging of Collagen, NAD(P)H and Flavin Autofluorescence in Mesenchymal Stem Cells Undergoing Trilineage Differentiation.","authors":"Jared M Campbell, Saabah B Mahbub, Ayad G Anwer, Abbas Habibalahi, Stan Gronthos, Sharon Paton, Shane T Grey, Lindsay E Wu, Robert B Gilchrist, Ewa M Goldys","doi":"10.3390/cells13201731","DOIUrl":"https://doi.org/10.3390/cells13201731","url":null,"abstract":"<p><p>Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495924","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201727
Nadine Nagy, Kathryn S Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C Reghupaty, Thomas N Wight, Robert B Vernon, Rebecca L Hull-Meichle, Payton Marshall, Carlos O Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D Paladini, Stavros Garantziotis, Joshua W Knowles, Paul L Bollyky
{"title":"Hymecromone Promotes Longevity and Insulin Sensitivity in Mice.","authors":"Nadine Nagy, Kathryn S Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C Reghupaty, Thomas N Wight, Robert B Vernon, Rebecca L Hull-Meichle, Payton Marshall, Carlos O Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D Paladini, Stavros Garantziotis, Joshua W Knowles, Paul L Bollyky","doi":"10.3390/cells13201727","DOIUrl":"https://doi.org/10.3390/cells13201727","url":null,"abstract":"<p><p>Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (<i>p</i> < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495961","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":"Pleiotropic Effects of Resveratrol on Aging-Related Cardiovascular Diseases-What Can We Learn from Research in Dogs?","authors":"Arkadiusz Grzeczka, Szymon Graczyk, Pawel Kordowitzki","doi":"10.3390/cells13201732","DOIUrl":"https://doi.org/10.3390/cells13201732","url":null,"abstract":"<p><p>Resveratrol (RES) is a polyphenol with natural anti-inflammatory and antioxidant properties. It is found in abundance in plants, i.e., grapes and mulberry fruit. In addition, synthetic forms of RES exist. Since the discovery of its specific biological properties, RES has emerged as a candidate substance not only with modeling effects on the immune response but also as an important factor in preventing the onset and progression of cardiovascular disease (CVD). Previous research provided strong evidence of the effects of RES on platelets, mitochondria, cardiomyocytes, and vascular endothelial function. In addition, RES positively affects the coagulation system and vasodilatory function and improves blood flow. Not only in humans but also in veterinary medicine, cardiovascular diseases have one of the highest incidence rates. Canine and human species co-evolved and share recent evolutionary selection processes, and interestingly, numerous pathologies of companion dogs have a human counterpart. Knowledge of the impact of RES on the cardiovascular system of dogs is becoming clearer in the literature. Dogs have long been recognized as valuable animal models for the study of various human diseases as they share many physiological and genetic similarities with humans. In this review, we aim to shed light on the pleiotropic effects of resveratrol on cardiovascular health in dogs as a translational model for human cardiovascular diseases.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495943","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201725
Chen-Chung Lin, Brandon F Law, Justin M Hettick
{"title":"Circular RNA <i>hsa_circ_0008726</i> Targets the <i>hsa-miR-206-3p</i>/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.","authors":"Chen-Chung Lin, Brandon F Law, Justin M Hettick","doi":"10.3390/cells13201725","DOIUrl":"https://doi.org/10.3390/cells13201725","url":null,"abstract":"<p><p>Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (<i>hsa/mmu</i>)-microRNA<i>(miR)-206-3p</i>, resulting in the activation of <i>mmu/hsa-miR-206-3p</i>-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate <i>hsa-miR-206-3p</i>. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate <i>hsa-miR-206-3p</i> in macrophages. The expression of candidate <i>hsa-miR-206-3p</i>-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced <i>hsa_circ_0008726</i> and its host gene transcript <i>DNAJB6</i>, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that <i>hsa-miR-206-3p</i> can bind to <i>hsa_circ_0008726</i>. The expressions of endogenous <i>hsa-miR-206-3p</i>, <i>hsa-miR-206-3p</i>-regulated <i>KLF4</i>, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of <i>hsa_circ_0008726</i> siRNAs or <i>hsa_circ_0008726</i> overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i> via induction of endogenous <i>hsa_circ_0008726/DNAJB6</i>, resulting in the upregulation of <i>hsa-miR-206-3p</i>-mediated regulations in macrophages.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495932","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201726
Carlo Airola, Maria Pallozzi, Eleonora Cesari, Lucia Cerrito, Leonardo Stella, Claudio Sette, Felice Giuliante, Antonio Gasbarrini, Francesca Romana Ponziani
{"title":"Hepatocellular-Carcinoma-Derived Organoids: Innovation in Cancer Research.","authors":"Carlo Airola, Maria Pallozzi, Eleonora Cesari, Lucia Cerrito, Leonardo Stella, Claudio Sette, Felice Giuliante, Antonio Gasbarrini, Francesca Romana Ponziani","doi":"10.3390/cells13201726","DOIUrl":"https://doi.org/10.3390/cells13201726","url":null,"abstract":"<p><p>Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies. They are characterized by a peculiar tumor microenvironment and dense vascularization. The importance of signaling between immune cells, endothelial cells, and tumor cells leads to the difficult recapitulation of a reliable in vitro HCC model using the conventional two-dimensional cell cultures. The advent of three-dimensional organoid tumor technology has revolutionized our understanding of the pathogenesis and progression of several malignancies by faithfully replicating the original cancer genomic, epigenomic, and microenvironmental landscape. Organoids more closely mimic the in vivo environment and cell interactions, replicating factors such as the spatial organization of cell surface receptors and gene expression, and will probably become an important tool in the choice of therapies and the evaluation of tumor response to treatments. This review aimed to describe the ongoing and potential applications of organoids as an in vitro model for the study of HCC development, its interaction with the host's immunity, the analysis of drug sensitivity tests, and the current limits in this field.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495960","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}
CellsPub Date : 2024-10-18DOI: 10.3390/cells13201729
Aurélie Cotten, Charlotte Jeanneau, Patrick Decherchi, Imad About
{"title":"Complement C5a Implication in Axonal Growth After Injury.","authors":"Aurélie Cotten, Charlotte Jeanneau, Patrick Decherchi, Imad About","doi":"10.3390/cells13201729","DOIUrl":"https://doi.org/10.3390/cells13201729","url":null,"abstract":"<p><p>Complement C5a protein has been shown to play a major role in tissue regeneration through interaction with its receptor (C5aR) on target cells. Expression of this receptor has been reported in the nervous system which, upon injury, has no treatment to restore the lost functions. This work aimed at investigating the Complement C5a effect on axonal growth after axotomy in vitro. Primary hippocampal neurons were isolated from embryonic Wistar rats. Cell expression of C5aR mRNA was verified by RT-PCR while its membrane expression, localization, and phosphorylation were investigated by immunofluorescence. Then, the effects of C5a on injured axonal growth were investigated using a 3D-printed microfluidic device. Immunofluorescence demonstrated that the primary cultures contained only mature neurons (93%) and astrocytes (7%), but no oligodendrocytes or immature neurons. Immunofluorescence revealed a co-localization of NF-L and C5aR only in the mature neurons where C5a induced the phosphorylation of its receptor. C5a application on injured axons in the microfluidic devices significantly increased both the axonal growth speed and length. Our findings highlight a new role of C5a in regeneration demonstrating an enhancement of axonal growth after axotomy. This may provide a future therapeutic tool in the treatment of central nervous system injury.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495934","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}