J Cell Physiol
· 2025 Jun · PMID 40495439
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Podocytes are highly specialized glomerular visceral epithelial cells critical for maintaining the structure and function of the glomerular filtration barrier. These cells adhere to the glomerular basement membrane (GBM)...Podocytes are highly specialized glomerular visceral epithelial cells critical for maintaining the structure and function of the glomerular filtration barrier. These cells adhere to the glomerular basement membrane (GBM) and envelop the outer surfaces of the glomerular capillaries to prevent protein leakage during blood ultrafiltration. The GBM is a dense network of extracellular matrix composed of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. In this study, we investigated the protective effect of a heparanase inhibitor on puromycin aminonucleoside (PAN)-induced podocyte injury. Our results demonstrate that PAN treatment significantly disrupted the cytoskeletal architecture of cultured podocytes, reducing the formation of focal adhesions and stress fibers. Interdigitating intercellular junctions were replaced by dot-like structures with accumulated filamentous actin. Co-treatment with the heparanase inhibitor PI-88 effectively prevented these PAN-induced cytoskeletal abnormalities. Furthermore, a BSA filtration assay revealed that PI-88 attenuated PAN-induced increases in podocyte monolayer permeability. Taken together, our findings suggest that heparanase inhibition protects against podocyte injury and may represent a potential therapeutic strategy for glomerular diseases.
Mansoori, B., A. Mohammadi, S. Naghizadeh, et al. 2020. "MiR-330 Suppresses EMT and Induces Apoptosis by Downregulating HMGA2 in Human Colorectal Cancer," Journal of Cellular Physiology 235, no. 2: 920-931. https://doi.o...Mansoori, B., A. Mohammadi, S. Naghizadeh, et al. 2020. "MiR-330 Suppresses EMT and Induces Apoptosis by Downregulating HMGA2 in Human Colorectal Cancer," Journal of Cellular Physiology 235, no. 2: 920-931. https://doi.org/10.1002/jcp.29007. The above article, published online on June 26, 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation by the publisher in response to concerns raised by third parties. Several flaws and inconsistencies have been identified between the described methodology and the presented results. Furthermore, the study's rationale and conclusions drawn are not supported by either the existing literature or the data extracted from The Cancer Genome Atlas (TCGA). Accordingly, the article is retracted as the editors consider its conclusions to be invalid. The authors have been informed of the decision of retraction but not available for a final confirmation.
Hirpara, D. G., H. P. Gajera, A. K. Patel, Z. A. Katakpara, and B. A. Golakiya, "Molecular Insights Into Development of Trichoderma Interfusants for Multistress Tolerance Enhancing Antagonism Against Sclerotium rolfsii S...Hirpara, D. G., H. P. Gajera, A. K. Patel, Z. A. Katakpara, and B. A. Golakiya, "Molecular Insights Into Development of Trichoderma Interfusants for Multistress Tolerance Enhancing Antagonism Against Sclerotium rolfsii Sacc." Journal of Cellular Physiology 234, no. 5 (2019): 7368-7383. https://doi.org/10.1002/jcp.27496. The above article, published online on 28 October 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath, and Wiley Periodicals LLC. A third party notified the journal of image duplications within Figure 2 of this article: Fu 9(a) had been re-used as Fu 21(a) and Fu 22 (12 DAI) had been re-used as Fu 23 (12 DAI). The third party also indicated that the Fu 21(a)/Fu 21(a) image had been re-used in another article by some of the same authors (Hirpara and Gajera [2018]; https://doi.org/10.1016/j.meegid.2018.09.005) and that all images describe different experimental conditions. Lastly, the third party also found evidence of duplicated datapoints within Table 1. An investigation by the publisher confirmed the duplication of images within Figure 8 and also found evidence of duplication and resizing of cellular sections between the Fu 21 and Fu 28 images in Figure S1. The authors responded to an inquiry by the publisher and provided what was labeled as original data. The authors confirmed that the FU 21 image in Figure 2 had been reused in another article but stated that the image was intended to provide background information on the purity of the fusant culture and that the duplication does not influence the results. The authors also confirmed the duplications of images in Figure 2 as well as the duplication in Figure S1, but they did not provide the original images for these experiments for verification by the publisher. A review of the original data found several duplicated datapoints that were not adequately explained and that some values reported in the original data did not match those in the published article. The retraction has been agreed to because of discrepancies between the published data and the original data, as well as the duplication of images within this article and with another published article, which fundamentally compromises the editors' confidence in the conclusions presented in the article. The authors disagree with the retraction.
The current hypothesis suggests that translation occurs in capacitated spermatozoa through mitochondrial ribosomes. Mitochondrial translation has several particularities, which rise some questions about how mitochondrial...The current hypothesis suggests that translation occurs in capacitated spermatozoa through mitochondrial ribosomes. Mitochondrial translation has several particularities, which rise some questions about how mitochondrial ribosomes can ensure sperm translation activity. Here, we aimed to elucidate if cytoplasmic translation occurs in mammalian spermatozoa. A bioinformatic workflow was performed to identify translation-related proteins in human spermatozoa and their association with cytoplasmic translation. The surface sensing of translation (SUnSET) method was used to measure translation activity in capacitated human and bovine spermatozoa. Two translation inhibitors, cycloheximide (CHX, cytoplasmic) and D-chloramphenicol (D-CP, mitochondrial) were used to identify which ribosomes were active in sperm. To spot newly synthesized proteins, puromycin-peptides were immunoprecipitated and analysed by mass spectrometry. A second approach was performed using translation inhibitors and analysing the sperm proteome by mass spectrometry. Bioinformatic analysis revealed that human spermatozoa possess 510 translation proteins, which were enriched for cytoplasmic mRNA translation. CHX decreased translation activity in mammalian sperm, whereas no effect was observed after D-CP treatment. Nine proteins were immunoprecipitated and identified as newly synthesized in capacitated bovine spermatozoa. CHX and D-CP decreased the level of 22 proteins that were replaced, or de novo translated during capacitation. New proteins were associated with relevant processes for sperm physiology. Both translation inhibitors decreased sperm rapid progressive motility and increased sperm immotility. Our results proved sperm translation occurs through cytoplasmic translation machinery in capacitated bovine and human spermatozoa. These results also support that sperm translation is required during capacitation to produce relevant proteins for sperm functions.
Hunter JJ, Del Valle L, Peruzzi F
… +1 more, Reiss K
J Cell Physiol
· 2025 May · PMID 40372980
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Biological systems do not exist in isolation. Analogous to the intricate design of a spider web, the metabolic adaptations propagated by glioblastoma cells are interlaced, creating a "defense mechanism" that increases th...Biological systems do not exist in isolation. Analogous to the intricate design of a spider web, the metabolic adaptations propagated by glioblastoma cells are interlaced, creating a "defense mechanism" that increases the likelihood of mutagenesis and proliferation, while mitigating stress-induced tumor cell death and immune evasion. Previous studies have observed the role of cardiolipin (CL) in the electron transport chain (ETC) function and several other intracellular signaling pathways. Our review provides a synopsis of the existing knowledge about CL in glioblastoma and its complex relationship with metabolic reprogramming at the subcellular level. Through a meticulous examination of CL defects due to its biogenesis and stress-induced modifications, we seek to elucidate the multifaceted connections between aberrant CL variants and the metabolic alterations that underlie glioblastoma progression. A comprehensive grasp of these mechanisms could provide future direction in designing chemotherapeutic agents that selectively target glioblastoma, are less harmful to normal cells, and therefore, may extend patient survival.
Zhou, Y., Wang, M., Zhang, J., Xu, P., and Wang, H. 2020. "MicroRNA-29a-3p Regulates Abdominal Aortic Aneurysm Development and Progression via Direct Interaction With PTEN." Journal of Cellular Physiology 235, no. 12: 94...Zhou, Y., Wang, M., Zhang, J., Xu, P., and Wang, H. 2020. "MicroRNA-29a-3p Regulates Abdominal Aortic Aneurysm Development and Progression via Direct Interaction With PTEN." Journal of Cellular Physiology 235, no. 12: 9414-9423, https://doi.org/10.1002/jcp.29746. The above article, published online on 7 May 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. Following an investigation by the publisher, it was determined that this article was accepted solely on the basis of a compromised peer review process. The editor has therefore decided to retract the article. The authors did not respond to requests for comment.
J Cell Physiol
· 2025 May · PMID 40349217
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Lysosomes are essential organelles degrading a wide range of substrates, maintaining cellular homeostasis, and regulating cell growth through nutrient and metabolic signaling. A key vulnerability of lysosomes is their me...Lysosomes are essential organelles degrading a wide range of substrates, maintaining cellular homeostasis, and regulating cell growth through nutrient and metabolic signaling. A key vulnerability of lysosomes is their membrane permeabilization (LMP), a process tightly linked to diseases including aging, neurodegeneration, lysosomal storage disorders, and cardiovascular disease. Research progress in the past few years has greatly improved our understanding of lysosomal repair mechanisms. Upon LMP, cells activate multiple membrane remodeling processes to restore lysosomal integrity, such as membrane invagination, tubulation, lipid patching, and membrane stabilization. These repair pathways are critical in preserving cellular stress tolerance and preventing deleterious inflammation and cell death triggered by lysosomal damage. This review focuses on the expanding mechanistic insights of lysosomal repair, highlighting its crucial role in maintaining cellular health and the implications for disease pathogenesis and therapeutic strategies.
The global impact of COVID-19, caused by SARS-CoV-2, has infected millions, including those with HIV-1. However, it is unclear if SARS-CoV-2 affects HIV-1 reactivation from latency. Here, we used the U1 cell line to expl...The global impact of COVID-19, caused by SARS-CoV-2, has infected millions, including those with HIV-1. However, it is unclear if SARS-CoV-2 affects HIV-1 reactivation from latency. Here, we used the U1 cell line to explore how SARS-CoV-2 infection affects HIV-1 reactivation from latency, employing real-time PCR assays and Western blot analysis. Our results show higher levels of HIV-1 RNA after SARS-CoV-2 infection. Importantly, we noticed enhanced reactivation of HIV-1 replication in cells infected with viruses carrying a deletion of amino acids R, R, A (RRAΔ) in the spike (S) protein, compared to infections with viruses carrying the wild-type S protein. This is involvement of host transcription factors like NFAT, NF-κB p65, Ap-1, and Sp-1, which facilitate HIV production via TCR-related pathways. Additionally, activation of p-TEFb pathways enhances transcription elongation, upregulates Jak/Stat pathways, leading to increased viral replication, while TLR pathways impact the host immune response. Furthermore, RRAΔ showed increased apoptotic activity through both extrinsic and intrinsic apoptotic signaling pathways compared to wild-type SARS-CoV-2. These indicate that SARS-CoV-2 infection could revive HIV-1 replication from latency. The deletion of amino acids RRA in the viral S protein might regulate further HIV-1 replication and apoptotic conditions, potentially benefiting HIV-1 survival.
Aubry A, Kebbe M, Naud P
… +3 more, Villeneuve L, Leblanc CA, Calderone A
J Cell Physiol
· 2025 Apr · PMID 40275768
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The 1-day-old neonatal rat heart contains two subpopulations of ventricular cardiomyocytes (NNVMs) that reenter the cell cycle in vitro and in vivo distinguished by the absence or de novo expression of the intermediate f...The 1-day-old neonatal rat heart contains two subpopulations of ventricular cardiomyocytes (NNVMs) that reenter the cell cycle in vitro and in vivo distinguished by the absence or de novo expression of the intermediate filament protein nestin. Furthermore, de novo nestin expression in NNVMs directly facilitated cell cycle reentry and elicited a morphological migratory phenotype. Previous studies have reported that ventricular cardiomyocytes failed to reenter the cell cycle following damage to the 7-day-old rodent heart. The present study tested the hypothesis that cell cycle reentry of one or both of the NNVM subpopulations of 7-day-old neonatal rat pups was compromised in vitro and/or in vivo following cardiac damage. Three-day treatment of 7-day-old NNVMs with the protein kinase C activator phorbol 12,13-dibutyrate and the serine/threonine p38α/β MAPK kinase inhibitor SB203580 facilitated cell cycle reentry into the S phase and G-M phase of the cell cycle. Two distinct subpopulations of 7-day NNVMs reentered the cell cycle, and the predominant subpopulation was distinguished by de novo nestin expression. Three days following the sham-operation of 7-day-old neonatal rat hearts, cell cycle reentry was detected exclusively in NNVMs lacking nestin expression. Partial apex resection of 7-day-old neonatal rat hearts led to the de novo appearance of nestin-NNVMs preferentially bordering the damaged region and a subpopulation reentered the S-phase and G-M phase of the cell cycle in the absence of p38α/β MAPK inhibition. By contrast, cell cycle reentry of nestin-NNVMs identified adjacent to the apex-resected region was significantly reduced. These data highlight the disparate in vivo regulation of the two subpopulations of NNVMs following damaged to the 7-day-old neonatal rat heart and reaffirm the premise that targeting the subpopulation of nestin-ventricular cardiomyocytes identified in the ischemically damaged adult mammalian heart represents a plausible first step to initiate cell cycle reentry.
Boulassel S, Schreier PCF, Melyshi AM
… +9 more, Berger J, Reinach PS, Jacob K, Boekhoff I, Breit A, Müller TD, Zierler S, Gudermann T, Khajavi N
J Cell Physiol
· 2025 Apr · PMID 40275767
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Transient receptor potential channel subfamily M member 7 (TRPM7) regulates cellular and systemic Mg homeostasis through its channel domain and induces protein phosphorylation via its kinase domain. We recently found tha...Transient receptor potential channel subfamily M member 7 (TRPM7) regulates cellular and systemic Mg homeostasis through its channel domain and induces protein phosphorylation via its kinase domain. We recently found that mice with selective deletion of Trpm7 in β-cells develop glucose intolerance and declines in insulin secretion, primarily due to the impaired enzymatic activity of this protein. Accumulating evidence suggests that Mg supplementation effectively mitigates the detrimental effects of TRPM7 disruption in various cell types. However, the impact of Mg supplementation on metabolic impairments caused by TRPM7 inactivation remains unclear. In the present study, we found that Mg supplementation significantly ameliorates glucose intolerance observed in high-fat-fed TRPM7 kinase-deficient mice (Trpm7). However, our ex vivo analysis of islets isolated from Trpm7 mice revealed that Mg supplementation does not enhance glucose-induced insulin secretion. Instead, the improvement appears to be partially driven by enhanced insulin sensitivity and increased β-cell proliferation. The pharmacological analysis in MIN6 cells showed that inhibiting TRPM7 with either NS8593 or VER155008 disrupts β-cell proliferation. These effects mimicked the phenotype seen in Trpm7 mice. We attribute this impairment to diminished ERK1/2 signaling, which suppressed PDX1 expression, while Mg supplementation in vitro partially restored ERK1/2 phosphorylation levels. Collectively, Mg supplementation enhances glucose metabolism in Trpm7 mice and mitigates the ERK1/2 signaling disruptions and proliferation arrest induced by TRPM7 inactivation in vitro. These findings provide compelling evidence that Mg supplementation can reverse the adverse metabolic and cellular phenotypes associated with the loss of TRPM7 function.
Glioma cells exhibit high invasiveness and have the ability to evade surgical resection, radiotherapy, and chemotherapy, which are major factors contributing to the challenges in effective treatment and recurrence. The u...Glioma cells exhibit high invasiveness and have the ability to evade surgical resection, radiotherapy, and chemotherapy, which are major factors contributing to the challenges in effective treatment and recurrence. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification, significantly contributing to the aggressive progression of glioblastoma (GBM). This study identified the E3 ubiquitin ligase CBLB as a crucial and abnormally regulated component of the UPS in GBM, noting its significant downregulation compared to normal brain tissue and its negative correlation with malignant phenotypes and poor prognosis. Experimental studies, both in vitro and in vivo, have shown that CBLB can inhibit the migration and invasion of GBM cells. Mechanistically, CBLB directly interacts with MAP3K9 through its RING domain, leading to K48-K63-linked polyubiquitination at the Lys 193 site, thereby promoting MAP3K9 proteasomal-mediated degradation. MAP3K9 downregulation suppresses MAPK-P38 pathway activation. This study identifies CBLB as a tumor suppressor that modulates the MAPK-P38 signaling pathway by promoting the polyubiquitination and degradation of MAP3K9, offering a new therapeutic approach for GBM treatment.
Orlov I, Lenglet G, Avondo C
… +3 more, Beattie JH, Kamel S, Korichneva I
J Cell Physiol
· 2025 Apr · PMID 40249000
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Vascular calcification (VC), a common pathological condition, is a strong predictor of cardiovascular events and associated mortality. Development and progression of VC heavily rely on vascular smooth muscle cells (VSMCs...Vascular calcification (VC), a common pathological condition, is a strong predictor of cardiovascular events and associated mortality. Development and progression of VC heavily rely on vascular smooth muscle cells (VSMCs) and are closely related to oxidative stress, inflammation, and remodelling of extracellular matrix (ECM). Copper (Cu), an essential microelement, participates in these processes, but its involvement in pathophysiology of VC and VSMCs physiology remains poorly investigated. In the present study, we analysed the impact of Cu on the calcification of human aortic primary VSMCs induced in vitro by treatment with high calcium and phosphate levels. Supplementation with physiological micromolar doses of Cu significantly reduced the amount of calcium deposited on VSMCs as compared to moderate deficiency, Cu restriction with chelators or Cu excess. Moreover, optimal concentrations of Cu ions increased protein production by VSMCs, stimulated their metabolic activity, inhibited alkaline phosphatase activity associated with cell-conditioned medium and cellular lysates, and prevented osteogenic differentiation of VSMCs. RNA-seq results indicated that high calcium and phosphate treatments activated many pathways related to oxidative stress and inflammation in VSMCs at the initial stage of calcification. At the same time, expression of VSMCs-specific markers and certain components of ECM were downregulated. Supplementation of calcifying cells with 10 μM Cu prevented most of the transcriptomic alterations induced by high calcium and phosphate while chelation-mediated restriction of Cu greatly aggravated them. In summary, physiological concentration of Cu impedes in vitro calcification of VSMCs, prevents their osteogenic transition and minimises early phenotypic alterations induced by high calcium and phosphate, thereby underlining the importance of Cu homeostasis for the physiology of VSMCs, one of the cornerstones of cardiovascular health. Our data suggest that features of Cu metabolism and its status should be considered when developing preventive and therapeutic approaches for cardiovascular diseases.
Cellular responses to mechanical stimulation are involved in tissue development and the maintenance of biological functions. Teeth function as receptors for mastication and occlusal pressure. During tooth development, th...Cellular responses to mechanical stimulation are involved in tissue development and the maintenance of biological functions. Teeth function as receptors for mastication and occlusal pressure. During tooth development, the tooth germ begins with an invagination of the epithelium, and its morphology matures through dynamic interactions between epithelial cells and mesenchymal cells, suggesting that mechanosensors may play an important role in this process. We analyzed the expression and function of Piezo1, a mechanically activated ion channel, during tooth development and clarified the involvement of Piezo1 in tooth morphogenesis. The expression of Piezo1 was observed in both the enamel organ and the surrounding mesenchymal cells at the early stage and in the ameloblasts and odontoblasts during enamel and dentin matrix formation. Yoda1, a Piezo1 activator, inhibited cell proliferation in mouse dental epithelial (mDE6) cells and E15 tooth germs, and suppressed cell migration in mDE6 cells. Meanwhile, GsMTx4, a Piezo1 inactivator, showed opposite results. Furthermore, in the organ culture of E15 tooth germs, the activation and inactivation of Piezo1 were found to affect the expression of ameloblast differentiation marker genes and control the arrangement of ameloblasts. Interestingly, the expression of E-cadherin was reduced in the cell membrane of ameloblasts at the cusp in the GsMTx4-treated tooth germs of organ culture, and enamel formation was significantly decreased. Yoda1-treated mDE6 cells showed upregulated E-cadherin expression, which was downregulated by calpain inhibitor. These findings suggest that Piezo1 may be involved in tooth morphogenesis during ameloblast development by playing an essential role in cell proliferation, migration, arrangement, differentiation, and mineralization.
Rai NK, Eberhardt DR, Balynas AM
… +4 more, MacEwen MJS, Bratt AR, Sancak Y, Chaudhuri D
J Cell Physiol
· 2025 Apr · PMID 40227803
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Mitochondrial Ca levels are regulated to balance stimulating respiration against the harm of Ca overload. Contributing to this balance, the main channel transporting Ca into the matrix, the mitochondrial Ca uniporter, ca...Mitochondrial Ca levels are regulated to balance stimulating respiration against the harm of Ca overload. Contributing to this balance, the main channel transporting Ca into the matrix, the mitochondrial Ca uniporter, can incorporate a dominant-negative subunit (MCUB). MCUB is homologous to the pore-forming subunit MCU, but when present in the pore-lining tetramer, inhibits Ca transport. Here, using cell lines deleted of both MCU and MCUB, we identify three factors that contribute to MCUB-dependent inhibition. First, MCUB protein requires MCU to express. The effect is mediated via the N-terminal domain (NTD) of MCUB. Replacement of the MCUB NTD with the MCU NTD recovers autonomous expression but fails to rescue Ca uptake. Surprisingly, mutations to MCUB that affect interactions with accessory subunits or the conduction pore all failed to rescue Ca uptake, suggesting the mechanism of inhibition may involve more global domain rearrangements. Second, using concatemeric tetramers with varying MCU:MCUB ratios, we find that MCUB incorporation does not abolish conduction, but rather inhibits Ca influx proportional to the amount of MCUB present in the channel. Reducing rather than abolishing Ca transport is consistent with MCUB retaining the highly-conserved selectivity filter DIME sequence. Finally, we apply live-cell Förster resonance energy transfer to establish that the endogenous stoichiometry is 2:2 MCU:MCUB. Taken together, our results suggest MCUB preferentially incorporates into nascent uniporters, and the amount of MCUB protein present linearly correlates with the degree of inhibition of Ca transport, creating a precise, tunable mechanism for cells to regulate mitochondrial Ca uptake.