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1.
J Cell Physiol ; 235(1): 166-175, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31180589

RESUMO

The pancreatic islets of Langerhans, mainly formed by glucagon-producing α-cells and insulin-producing ß-cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi-hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of α-cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic α-cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for α-cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in α-cell metabolism.

2.
J Cell Physiol ; 235(1): 151-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31187491

RESUMO

Slc25a17 is known as a peroxisomal solute carrier, but the in vivo role of the protein has not been demonstrated. We found that the zebrafish genome contains two slc25a17 genes that function redundantly, but additively. Notably, peroxisome function in slc25a17 knockdown embryos is severely compromised, resulting in an altered lipid composition. Along the defects found in peroxisome-associated phenotypic presentations, we highlighted that development of the swim bladder is also highly dependent on Slc25a17 function. As Slc25a17 showed substrate specificity towards coenzyme A (CoA), injecting CoA, but not NAD+ , rescued the defective swim bladder induced by slc25a17 knockdown. These results indicated that Slc25a17 acts as a CoA transporter, involved in the maintenance of functional peroxisomes that are essential for the development of multiple organs during zebrafish embryogenesis. Given high homology in protein sequences, the role of zebrafish Slc25a17 may also be applicable to the mammalian system.

3.
J Cell Physiol ; 235(1): 221-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31187497

RESUMO

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.

4.
J Cell Physiol ; 235(1): 185-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31190335

RESUMO

Cervical cancer (CC) is a prevalent malignancy in women, with the feature of metastasis and easy recurrence is responsible for a large proportion of global cancer deaths. Radiotherapy is one of the common treatment tools for CC patients with unresectable tumors. However, radio-resistance in patients could be a major reason for recurrence. Therefore, it is of significance to tunnel the molecular mechanism of radio-resistance in CC. MicroRNAs (miRNAs) are increasingly reported in the regulation of cancer progression and cellular response to radiotherapy and chemotherapy. miR-4429 is a newly discovered miRNA acting as a tumor-suppressor gene in multiple cancers, but its function in CC has never been explored yet. The current study tried to explore the role of miR-4429 in cell radio-sensitivity in CC. First, we validated the downregulation of miR-4429 in CC cells. Importantly, the association of miR-4429 with radio-resistance was validated by identifying the downregulation of miR-4429 in radio-resistant CC cells. Gain- and loss-of-function assays validated that miR-4429 sensitized CC cells to irradiation. Through bioinformatics tools, RAD51 recombinase (RAD51) was identified to be a target for miR-4429. RAD51 is known to be a crucial regulator for DNA damage repair and has been reported to influence cell radio-resistance in cancers, including in CC. Luciferase reporter assay confirmed the interaction between miR-4429 and RAD51. Finally, rescue assays indicated that miR-4429 promoted CC cell radio-sensitivity through RAD51. Consequently, our study showed that miR-4429 sensitized CC cells to irradiation by targeting RAD51, providing a potential therapeutic target for CC patients.

5.
J Cell Physiol ; 235(1): 6-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31192453

RESUMO

MicroRNAs (miRNAs) are small noncoding RNAs about 19-22 nucleotides in length. Growing evidence has reported the significant role of miRNAs in various cancer-associated biological processes, such as proliferation, differentiation, apoptosis, metabolism, invasion, metastasis, and drug resistance. However, most studies focus on the targets of some individual miRNAs; the interactive and global functions of diverse miRNAs are still unclear and the phenomenon of the gathering of miRNAs in clusters has always been ignored. On the other hand, the fact that a single miRNA may regulate many genes and that numerous mRNAs are regulated by the same miRNA also makes it imperative to further study the cooperating characteristics of miRNAs in cancer. MiR-23a-27a-24-2 is located in the human chromosome 9q22, forming three mature miRNAs: miR-23a, miR27a, and miR-24, which are expressed abnormally in many malignant tumors. This review aims to summarize the interactive functions of miRNAs in miR-23a-27a-24-2 clusters in cancer from the perspectives of the regulation network, tumor microenvironment, and targeted therapy.

6.
J Cell Physiol ; 235(1): 304-316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206189

RESUMO

Adipogenesis, the developmental process of progenitor-cell differentiating into adipocytes, leads to fat metabolic disorders. Alternative splicing (AS), a ubiquitous regulatory mechanism of gene expression, allows the generation of more than one unique messenger RNA (mRNA) species from a single gene. Till now, alternative splicing events during adipogenesis from human mesenchymal stem cells (hMSCs) are not yet fully elucidated. We performed RNA-Seq coupled with bioinformatics analysis to identify the differentially expressed AS genes and events during adipogenesis from hMSCs. A global survey separately identified 1262, 1181, 1167, and 1227 ASE involved in the most common types of AS including cassette exon, alt3, and alt5, especially with cassette exon the most prevalent, at 7, 14, 21, and 28 days during adipogenesis. Interestingly, 122 differentially expressed ASE referred to 118 genes, and the three genes including ACTN1 (alt3 and cassette), LRP1 (alt3 and alt5), and LTBP4 (cassette, cassette_multi, and unknown), appeared in multiple AS types of ASE during adipogenesis. Except for all the identified ASE of LRP1 occurred in the extracellular topological domain, alt3 (84) in transmembrane domain significantly differentially expressed was the potential key event during adipogenesis. Overall, we have, for the first time, conducted the global transcriptional profiling during adipogenesis of hMSCs to identify differentially expressed ASE and ASE-related genes. This finding would provide extensive ASE as the regulator of adipogenesis and the potential targets for future molecular research into adipogenesis-related metabolic disorders.

7.
J Cell Physiol ; 235(1): 267-280, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206674

RESUMO

Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na+ , K+ -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma.

8.
J Cell Physiol ; 235(1): 17-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206681

RESUMO

SPTBN1 is a dynamic intracellular nonpleckstrin homology-domain protein, functioning as a transforming growth factor-ß signal transducing adapter protein which is necessary to form Smad3/Smad4 complex. Recently SPTBN1 is considered to be associated with many kinds of cancers. SPTBN1 expression and function differ between different tumor states or types. This review summarizes the recent advances in the expression patterns of SPTBN1 in cancers, and in understanding the mechanisms by which SPTBN1 affects the occurrence, progression, and metastasis of cancer. Identifying SPTBN1 expression and function in cancers will contribute to the clinical diagnosis and treatment of cancer and the investigation of anticancer drugs.

9.
J Cell Physiol ; 235(1): 294-303, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206688

RESUMO

Diabetes is a leading cause of microvascular complications, such as nephropathy and retinopathy. Recent studies have proposed that hyperglycemia-induced endothelial cell dysfunction is modulated by mitochondrial stress. Therefore, our experiment was to detect the upstream mediator of mitochondrial stress in hyperglycemia-treated endothelial cells with a focus on macrophage-stimulating 1 (Mst1) and mitochondrial fission. Our data illuminated that hyperglycemia incubation reduced cell viability, as well as increased apoptosis ratio in endothelial cell, and this alteration seemed to be associated with Mst1 upregulation. Inhibition of Mst1 via transfection of Mst1 siRNA into an endothelial cell could sustain cell viability and maintain mitochondrial function. At the molecular levels, endothelial cell death was accompanied with the activation of mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial fission. Genetic ablation of Mst1 could reduce mitochondrial oxidative injury, block mitochondrial apoptosis, and repress mitochondrial fission. Besides, we also found Mst1 triggered mitochondrial dysfunction as well as endothelial cell damage through augmenting JNK pathway. Suppression of JNK largely ameliorated the protective actions of Mst1 silencing on hyperglycemia-treated endothelial cells and sustain mitochondrial function. The present study identifies Mst1 as a primary key mediator for hyperglycemia-induced mitochondrial damage and endothelial cell dysfunction. Increased Mst1 impairs mitochondrial function and activates endothelial cell death via opening mitochondrial death pathway through JNK.

10.
J Cell Physiol ; 235(1): 65-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206697

RESUMO

Head and neck cancer (HNC) is the six most common malignancy worldwide leading to more than 350,000 deaths annually. Despite recent advances in treatment modalities for these patients, there has been only a slight improvement of prognosis. As cancer stem cells (CSCs) have been implicated in tumor cell survival, progression, and response to therapy, the identification of this tumor subpopulation would have important therapeutic and prognostic implications. In this structured appraisal of the literature, Embase, PubMed, and Ovid were searched for publications that investigated CSC markers of HNC in humans. The search was conducted under the PRISMA guidelines with clear inclusion and exclusion criteria for articles published in the last two decades. The review process resulted in the identification of some key CSC-associated molecules such as CD44, ALDH1, CD133, Oct3/4, Nanog, and Sox2, although a single common CSC sorting marker could not be found. These biomarkers were identified in a range of HNCs but the most common one was squamous cell carcinoma (SCC), predominantly oral SCC. Patient cohorts were of variable size (3-195 individuals) and the most common technique used for detection was immunohistochemistry. Some of the molecules were associated with poor prognosis and may be able to inform the choice of appropriate treatment for these patients.

11.
J Cell Physiol ; 235(1): 176-184, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31210352

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is a clinically familiar disease, which possesses a great negative impact on human health. But, the effective treatment is still absent. MicroRNAs (miRNAs) have been testified to play a momentous role in MIRI. The purpose of the study aimed to probe the functions of miR-132 in oxygen and glucose deprivation (OGD)-evoked injury in H9c2 cells. miR-132 expression in H9c2 cells accompanied by OGD disposition was evaluated via real-time quantitative polymerase chain reaction. After miR-132 mimic and inhibitor transfections, the impacts of miR-132 on OGD-affected H9c2 cell viability, apoptosis, cell cycle, and the interrelated factors were appraised by exploiting cell counting kit-8, flow cytometry, and western blot analysis. FOXO3A expression was estimated in above-transfected cells, meanwhile, the correlation between miR-132 and FOXO3A was probed by dual-luciferase report assay. Ultimately, above mentioned cell processes were reassessed in H9c2 cells after preprocessing OGD administration and transfection with si-FOXO3A and si-NC plasmids. We got that OGD disposition obviously enhanced miR-132 expression in H9c2 cells. Overexpressed miR-132 evidently reversed OGD-evoked cell viability repression and apoptosis induction in H9c2 cells. In addition, overexpressed miR-132 mitigated OGD-evoked G0/G1 cell arrest by mediating p21, p27, and cyclin D1 expression. Repression of FOXO3A was observed in miR-132 mimic-transfected cells, which was also predicated as a direct gene of miR-132. We discovered that silenced FOXO3A alleviated OGD-evoked cell injury in H9c2 cells via facilitating cell viability, hindering apoptosis and restraining cell arrest at G0/G1 phase. In conclusion, these investigations corroborated that miR-132 exhibited the protective impacts on H9c2 cells against OGD-evoked injury via targeting FOXO3A.

12.
J Cell Physiol ; 235(1): 328-338, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31210354

RESUMO

MicroRNAs (miRNAs), the potential regulator of adipogenesis, markedly characterized by lipid droplet (LD) formation, play an important role in progenitor-cell differentiation into adipocytes. In recent years, it has excited interests in regulation of miRNAs in adipogenesis. However, no study is available, to our knowledge, regarding the expression of miRNAs on LD formation. Our study provides the first insight into the expression profiling of the miRNA targeting messenger RNAs (mRNAs) involving with LD formation during adipogenesis from human mesenchymal stem cells by RNA-Seq transcriptome technique. It showed that 39, 105, 194, and 112 differentially expressed miRNA appeared at 7, 14, 21, and 28 days, respectively, for LD formation during adipogenesis. Nineteen miRNAs targeted 35 mRNA associated with LDs formation. Except for the known miRNA hsa-miR-1908 regulating adipogenesis, five miRNAs, including hsa-miR-146a-3p, hsa-miR-4495, hsa-miR-4663, hsa-miR-6069, and hsa-miR-675-3p are the latest potential biomarkers for LD formation, targeting ACSL1, APOB, METTL7A, PLIN1, and PLIN4. A comprehensive transcriptome profiling of miRNA reveals the regulatory relationship between miRNA and mRNA relating to LD formation during adipogenesis. Such candidates may represent biomarkers and therapeutic targets for metabolic syndromes like obesity, type-2 diabetes, steatosis, atherosclerosis, and osteoporosis.

13.
J Cell Physiol ; 235(1): 281-293, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31215024

RESUMO

The inflammatory microenvironment in the joints is one of the critical issues during osteoarthritis (OA) and also the main factor that may aggravate symptoms. Under inflammatory microenvironment, M1 macrophages are activated and produce large numbers of proinflammatory mediators, leading to the production of degradative enzymes, the disturbance of chondrocyte apoptosis and cartilage catabolic processes, and finally the deterioration of OA. In the present study, we reveal that the overexpression of osteopontin (OPN), a cytokine, and a matrix protein involved in arthritis and chondrocyte apoptosis in OA, could exacerbate the inflammatory microenvironment in OA via promoting the production of proinflammation cytokines and the levels of degradative enzymes in M1 macrophages, therefore, enhancing the cytotoxicity of M1 macrophage on chondrocytes. XIST expression significantly increases in OA tissue specimens. XIST serves as a competing endogenous RNA for miR-376c-5p to compete with OPN for miR-376c-5p binding, thus counteracting miR-376c-5p-mediated OPN suppression. XIST knockdown could improve the inflammatory microenvironment in OA via acting on M1 macrophages, subsequently affecting the apoptosis of cocultured chondrocytes. miR-376c-5p inhibition exerts an opposing effect on M1 macrophages and cocultured chondrocytes, as well as significantly reverses the effect of XIST knockdown. As a further confirmation, XIST and OPN mRNA expression significantly increased in OA tissues and was positively correlated in tissue samples. In summary, we provide a novel mechanism of macrophages and the inflammatory microenvironment affecting chondrocyte apoptosis. XIST and OPN might be potential targets for OA treatment, which needs further in vivo experimental confirmation.

14.
J Cell Physiol ; 235(1): 317-327, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31215035

RESUMO

Cardiomyocyte function and viability are highly modulated by mammalian Ste20-like kinase 1 (Mst1)-Hippo pathway and mitochondria. Mitophagy, a kind of mitochondrial autophagy, is a protective program to attenuate mitochondrial damage. However, the relationship between Mst1 and mitophagy in septic cardiomyopathy has not been explored. In the present study, Mst1 knockout mice were used in a lipopolysaccharide (LPS)-induced septic cardiomyopathy model. Mitophagy activity was measured via immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay. Pathway blocker and small interfering RNA were used to perform the loss-of-function assay. The results demonstrated that Mst1 was rapidly increased in response to LPS stress. Knockout of Mst1 attenuated LPS-mediated inflammation damage, reduced cardiomyocyte death, and improved cardiac function. At the molecular levels, LPS treatment activated mitochondrial damage, such as mitochondrial respiratory dysfunction, mitochondrial potential reduction, mitochondrial ATP depletion, and caspase family activation. Interestingly, in response to mitochondrial damage, Mst1 deletion activated mitophagy which attenuated LPS-mediated mitochondrial damage. However, inhibition of mitophagy via inhibiting parkin mitophagy abolished the protective influences of Mst1 deletion on mitochondrial homeostasis and cardiomyocyte viability. Overall, our results demonstrated that septic cardiomyopathy is linked to Mst1 upregulation which is followed by a drop in the protective mitophagy.

15.
J Cell Physiol ; 235(1): 31-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31215038

RESUMO

Cytotoxic small-molecule drugs have a major influence on the fate of antibody-drug conjugates (ADCs). An ideal cytotoxic agent should be highly potent, remain stable while linked to ADCs, kill the targeted tumor cell upon internalization and release from the ADCs, and maintain its activity in multidrug-resistant tumor cells. Lessons learned from successful and failed experiences in ADC development resulted in remarkable progress in the discovery and development of novel highly potent small molecules. A better understanding of such small-molecule drugs is important for development of effective ADCs. The present review discusses requirements making a payload appropriate for antitumor ADCs and focuses on the main characteristics of commonly-used cytotoxic payloads that showed acceptable results in clinical trials. In addition, the present study represents emerging trends and recent advances of payloads used in ADCs currently under clinical trials.

16.
J Cell Physiol ; 235(1): 26-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31219174

RESUMO

Microtubule-interfering agents have been very useful both as biological tools in studying mitosis and as chemotherapeutic agents against cancer. It remains poorly understood how these agents converge on the spindle assembly checkpoint (SAC) to halt mitotic progression, while inhibiting microtubule dynamics by different mechanisms. Cells arrested at mitosis by various microtubule-interfering agents exhibit strikingly different defects in the mitotic spindle. However, all the arrested cells possess the 3F3/2 phosphoepitope at the sister kinetochores of chromosomes, indicating the decrease of tension across the paired kinetochores. In addition, microtubule-interfering agents result in a comparable reduction in the distance between sister kinetochores, suggesting that these agents decrease interkinetochore tension to similar degrees. Here, we discuss recent progress that suggests impairment of kinetochore-microtubule attachment and reduction of interkinetochore tension as common mechanisms underlying the persistent SAC activation in response to diverse microtubule-interfering agents.

17.
J Cell Physiol ; 235(1): 194-209, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31219187

RESUMO

The transformation abilities of CD44s and CD44v6 in normal intestinal epithelial cells have not yet been reported. Herein, we established both CD44s and CD44v6 overexpressing stable clones from rat IEC-6 cells and demonstrated that the CD44v6 clones had higher saturation density and anchorage independence. Additionally, CD44v6 clones were more resistant to oxaliplatin and irinotecan which might be attributed to a significantly increased B-cell lymphoma 2 level and a reduced DNA damage response in these cells. Moreover, c-Met and vascular endothelial growth factor receptor 2 signalings were involved in modulating the saturation density in CD44v6 clones. Interestingly, higher activation of both AKT and extracellular-signal-regulated kinase (ERK) were detected in CD44v6 clones which might account in part for the cell density-independent nuclear localization of Yes-associated protein (YAP). To no surprise, increases of both saturation density and anchorage independence in CD44v6 clones were markedly diminished by PI3K, AKT, MEK, and ERK inhibitors as well as YAP knockdown. By contrast, overexpression of a constitutively active YAP robustly increased the aforementioned phenotypes in IEC-6 cells. Collectively, our results suggest that upregulation of CD44v6, but not CD44s, induces the transformation of normal intestinal epithelial cells possibly via activating the c-Met/AKT/YAP pathway which might also explain the important role of CD44v6 in the initiation of various carcinomas.

18.
J Cell Physiol ; 235(1): 421-428, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31222739

RESUMO

Despite the response to the receptor activator of nuclear factor κ-Β ligand (RANKL), a study has reported that lipopolysaccharide (LPS) could induce RAW264.7 linage osteoclastic differentiation. However, on the contrary, another study recently showed that the LPS-induced multinuclear cells from RAW264.7 did not express osteoclastic functions. Interestingly, in our previous study, we found that RAW264.7 cells pretreated with 10 ng LPS plus macrophage-colony stimulating factor did not show any effects for enhancing RANKL-induced osteoclastic cell differentiation. Therefore, in our current study, we aim to investigate the oteoclastogesis induction ability and efficacy of LPS in the RAW264.7 cell line and relevant molecular signaling. The osteoclastogenic activity of LPS-treated RAW264.7 linage was studied by bone resorption pits and fibrous actin study. Besides that, through polymerase chain reaction and western blot, we showed that the transcriptional factor c-Fos and Nfatc1 might be associated with LPS-induced osteoclastogenesis. Overall, the results of our current study showed positive proof for osteoclast generation from LPS-independent treatment, as well as established an optimal and efficient method for this process.

19.
J Cell Physiol ; 235(1): 74-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31222740

RESUMO

Multiple modalities for lung cancer therapy have emerged in the past decade, whereas their clinical applications and survival-beneficiary is little known. Vaccination with dendritic cells (DCs) or DCs/cytokine-induced killer (CIK) cells has shown limited success in the treatment of patients with advanced non-small-cell lung cancer. To evaluate and overcome these limitations in further studies, in the present review, we sum up recent progress about DCs or DCs/CIKs-based approaches for preclinical and clinical trials in patients with lung cancer and discuss some of the limited therapeutic success. Moreover, this review highlights the need to focus future studies on the development of new approaches for successful immunotherapy in patients with lung cancer.

20.
J Cell Physiol ; 235(1): 465-479, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31222743

RESUMO

The interaction between nanohydroxyapatite (HAP) and smooth muscle cells is an important step in vascular calcification. However, the effect of the shape of HAP on adhesion and endocytosis to aortic smooth muscle cells has been rarely reported. Four different morphological HAP crystals (H-Rod, H-Needle, H-Sphere, and H-Plate) were selected to interact with rat aortic smooth muscle cells (A7R5). Fluorescence-labeled HAP was used to detect crystal adhesion and endocytosis and then pretreated with different endocytic inhibitors to explore the pathway of endocytotic crystals. The distribution of crystals inside and outside the cells and the crystal localization in lysosomes was observed through laser confocal microscopy. The effect of crystal on the cell cycle and the changes in the expression of phosphatidylserine, osteopontin, α-actin, core binding factor alpha 1, and osterix on the surface of A7R5 cells were detected. The adhesion and endocytosis of HAP on A7R5 cells were closely related to crystal shapes and ranked as follows: H-Plate > H-Sphere > H-Needle > H-Rod. H-Sphere and H-Needle were internalized into the cells mainly via the clathrin-mediated pathway, whereas H-Plate and H-Rod were internalized into the cells mainly via macropinocytosis. The endocytosed nano-HAP was mainly distributed in the cell lysosome. The adhesion and endocytosis of HAP to A7R5 cells were positively correlated with the specific surface area, and contact area of HAP and negatively correlated with the absolute value of Zeta and contact angle of HAP. This study provided insights into the effect of crystal morphology on vascular calcification and its mechanism.

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