scholarly journals Inhibition of TRPC6 Signal Pathway Alleviates Podocyte Injury Induced by TGF-β1

2017 ◽  
Vol 41 (1) ◽  
pp. 163-172 ◽  
Author(s):  
Haiting Huang ◽  
Yanwu You ◽  
Xu Lin ◽  
Chunrong Tang ◽  
Xiangjun Gu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Critical Role ◽  
Signal Pathway ◽  
Control Group ◽  
Caspase 9 ◽  
Podocyte Injury ◽  
Apoptosis Rate ◽  
Tgf Β1

Background/Aims: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. Methods: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo. Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-β1 treatment; TGF-β1 with TRPC6 knockdown and TGF-β1 without TRPC6 knockdown. Real time RT-PCR and Western blot analysis were employed to determine the mRNA and protein of expression of nephrin, desmin and caspase-9, respectively. Flow cytometry was used to examine the apoptotic rate of podocytes and DAPI fluorescent staining was used to determine apoptotic morphology. Results: In vivo experiment, adriamycin significantly upregulated the protein expression of TGF-β1, TRPC6, desmin and caspase-9, and decreased nephrin. Consistent with the latter results, in vitro experiment mRNA and protein expression of desmin and caspase-9 was increased in cultured TGF-β1-treated podocytes, whereas nephrin was declined as compared with the control group. Importantly, TRPC6 knockdown significantly attenuated the upregulated desmin and caspase-9, and alleviated impairment of nephrin induced by TGF-β1. Moreover, typical morphologic features were presented in apoptotic podocytes. The number of apoptotic podocytes was increased after exposure to TGF-β1 and this was alleviated after TRPC6 knockdown. TRPC6 knockdown also decreased an apoptosis rate of TGF-β1-treated podocytes. Note that negative TRPC6 transfection control failed to alter an increase of the apoptosis rate in TGF-β1-treated podocytes. Conclusions: TGF-β1 induced by glomerulosclerosis impairs the protein expression of nephrin and amplifies the protein expression of desmin and caspase -9 via TRPC6 signal pathway. Inhibition of TRPC6 alleviates these changes in podocytes-treated with TGF-β1 and attenuated apoptosis of podocytes. Our data suggest that TRPC6 signal plays an important role in mediating TGF-β1-induced podocyte injury via nephrin, desmin and caspase-9. Results of the current study also indicate that blocking TRPC6 signal pathway has a protective effect on podocyte injury. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of podocyte injury observed in glomerulosclerosis.

scholarly journals Role of MiR-155 Signal Pathway in Regulating Podocyte Injury Induced by TGF-β1

2017 ◽  
Vol 42 (4) ◽  
pp. 1469-1480 ◽  
Author(s):  
Xu Lin ◽  
Xintng Zhen ◽  
Haiting Huang ◽  
Haohao Wu ◽  
Yanwu You ◽  
...  
Keyword(s):  
Protein Expression ◽  
Antisense Oligonucleotides ◽  
Negative Control ◽  
Signal Pathway ◽  
Caspase 9 ◽  
Podocyte Injury ◽  
Apoptosis Rate ◽  
Mrna And Protein Expression ◽  
Tgf Β1

Background/Aims: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of miR-155 on podocyte injury induced by TGF-β1 and to determine further molecular mediators involved in the effects of miR-155. Methods: Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-β1 treatment; TGF-β1 with miR-155 knockdown [using antisense oligonucleotides against miR-155 (ASO-miR-155)] and TGF-β1 with negative control antisense oligonucleotides (ASO-NC). Real time RT-PCR and Western blot analysis were employed to determine the mRNA and protein expression of nephrin, desmin and caspase-9, respectively. Flow cytometry was used to examine the apoptotic rate of podocytes and DAPI fluorescent staining was used to determine apoptotic morphology. In addition, we examined the levels of miR-155, TGF-β1, nephrin, desmin and caspase-9 in glomerular tissues of nephropathy induced by intravenous injections of adriamycin in rats. Results: mRNA and protein expression of desmin and caspase-9 was increased in cultured TGF-β1-treated podocytes, whereas nephrin was decreased as compared with the control group. Importantly, miR-155 knockdown significantly attenuated upregulation of desmin and caspase-9, and alleviated impairment of nephrin induced by TGF-β1. Moreover, the number of apoptotic podocytes was increased after exposure to TGF-β1 and this was alleviated after miR-155 knockdown. Knocking down miR-155 also decreased an apoptosis rate of TGF-β1-treated podocytes. Note that negative control antisense oligonucleotides failed to alter an increase of the apoptosis rate in TGF-β1-treated podocytes. Consistent with in vitro results, expression of miR-155, TGF-β1, desmin and caspase-9 was increased and nephrin was decreased in glomerular tissues with nephropathy in vivo experiments. Conclusions: TGF-β1 impairs the protein expression of nephrin and amplifies the protein expression of desmin and caspase -9 via miR-155 signal pathway. Inhibition of miR-155 alleviates these changes in podocytes-treated with TGF-β1 and attenuated apoptosis of podocytes. Our data suggest that miR-155 plays a role in mediating TGF-β1-induced podocyte injury via nephrin, desmin and caspase-9. Results of the current study also indicate that blocking miR-155 signal has a protective effect on podocyte injury. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of podocyte injury observed in glomerulosclerosis.

scholarly journals Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zetao Chen ◽  
Yihong Chen ◽  
Yan Li ◽  
Weidong Lian ◽  
Kehong Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
Critical Role ◽  
Glioma Stem Cells ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Smad Pathway ◽  
Tgf Β1

AbstractGlioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-β1 gene, upregulated TGF-β1 expression, and ultimately activated the TGF-β/smad pathway. Silencing TGF-β1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-β/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients.

scholarly journals Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

2020 ◽  
Author(s):  
Guiqing Zhou ◽  
Jianhui Liu ◽  
Xiangyang Li ◽  
Yujian Sang ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Silica Nanoparticles ◽  
Caspase 3 ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Underlying Mechanisms

Abstract Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

scholarly journals MDM2 mediates fibroblast activation and renal tubulointerstitial fibrosis via a p53-independent pathway

2017 ◽  
Vol 312 (4) ◽  
pp. F760-F768 ◽  
Author(s):  
Chen Ye ◽  
Hui Tang ◽  
Zheng Zhao ◽  
Chun-Tao Lei ◽  
Chao-Qun You ◽  
...  
Keyword(s):  
Critical Role ◽  
Tubulointerstitial Fibrosis ◽  
Podocyte Injury ◽  
Fibroblast Activation ◽  
Downstream Signaling ◽  
Renal Tubulointerstitial Fibrosis ◽  
Inflammatory Processes ◽  
Tgf Β1

It is well recognized that murine double minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. It is also reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and Western blotting we confirmed that MDM2 is upregulated in the tubulointerstitial compartment in patients with TIF and unilateral urethral obstruction (UUO) mice, which mainly originates from myofibroblasts. Consistently, in vitro MDM2 is increased in TGF-β1-treated fibroblasts, one of the major sources of collagen-producing myofibroblasts during TIF, along with fibroblast activation. Importantly, genetic deletion of MDM2 significantly attenuates fibroblast activation. We then analyzed the possible downstream signaling of MDM2 during fibroblast activation. p53-dependent pathway is the classic downstream signaling of MDM2, and Nutlin-3 is a small molecular inhibitor of MDM2-p53 interaction. To our surprise, Nutlin-3 could not ameliorate fibroblast activation in vitro and TIF in UUO mice. However, we found that Notch1 signaling is attenuated during fibroblast activation, which could be markedly rescued by MDM2 knockdown. Overexpression of intracellular domain of Notch1 (NICD) by plasmid could obviously minimize fibroblast activation induced by TGF-β1. In addition, the degradation of NICD is strikingly suppressed by PYR-41, an inhibitor of ubiquitin-activating enzyme E1, and proteasome inhibitor MG132. Taken together, our findings provide the first evidence that MDM2 is involved in fibroblast activation and TIF, which associates with Notch1 ubiquitination and proteasome degradation.

scholarly journals Assemble Flavone of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signal Pathway

2020 ◽  
Author(s):  
Shuyuan Li ◽  
Hongliang zhou ◽  
Chenghu Hu ◽  
Jiabao Yang ◽  
Yue Li ◽  
...  
Keyword(s):  
Bone Graft ◽  
Signal Pathway ◽  
Autogenous Bone ◽  
Control Group ◽  
Sprague Dawley ◽  
Induced Membrane ◽  
Membrane Technique ◽  
Rhizoma Drynariae

Abstract Background: Assemble Flavone of Rhizoma Drynariae (AFRD) is not only the extract of Rhizoma Drynariae, but also the effective component of Qianggu capsule, which is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good results. Purpose of this trial was to explore effects of AFRD on bone graft mineralization and osteoblast differentiation in Masquelet induced membrane in rats.Methods: Twenty male Sprague-Dawley rats aged 10-12 weeks were randomLy divided into AFRD group (n=10) and control group (n=10). Critical-sized defects model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) was implanted into the defect of femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 10 weeks of bone grafting, bone tissue in the bone graft area was examined by X-ray, Micro-CT and hematoxylin-eosin (HE) staining to evaluate the growth of the bone graft. Serums of the two groups of rats were extracted respectively, and these serums were used to culture osteoblasts in vitro. CKK8 method, Alkaline phosphatase (ALP) staining, Western blot and RT-PCR and other methods were used to evaluate the effects of AFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signal pathway.Results: In vivo experiment showed that the growth and mineralization effect of bone graft in AFRD group was better. In vitro experiment showed that osteoblasts proliferated faster, ALP activity was higher, number of mineralized nodules was more, and expression of proteins related to Wnt/β-catenin signal pathway and osteogenesis were more in AFRD group.Conclusions: AFRD can promote mineralization of bone graft and differentiation of osteoblasts during the bone graft growth period of induced membrane technique, which is related to the activation of Wnt/ β-catenin signal pathway.

scholarly journals NQO1 Alleviates Renal Fibrosis by Inhibiting TLR4/NF-κB and TGF-β/Smad Signaling Pathway in Diabetic Nephropathy

2021 ◽  
Author(s):  
Duojun Qiu ◽  
Shan Song ◽  
Yawei Bian ◽  
Chen Yuan ◽  
wei zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protein Expression ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Renal Tubular ◽  
Tgf Β1 ◽  
Cytokines Secretion ◽  
Pro Inflammatory Cytokines

Abstract Background: Diabetic nephropathy is one of the main complications of diabetes, inflammation and fibrosis play an important role in its progress. NAD (P) H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and toxic quinone damage. In present study, we aimed to investigate the protective effects and underlying mechanisms of NQO1 on diabetes-induced renal inflammation and fibrosis. Methods: In vivo, adeno-associated virus serotype 9 was used to infect the kidneys of type 2 diabetes model db/db mice to overexpress NQO1. In vitro, human renal tubular epithelial cells (HK-2) transfected with NQO1 pcDNA were cultured in high glucose. The gene and protein expression were assessed by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemical staining. Mitochondrial reactive oxygen species was detected by MitoSox red. Result: Our study revealed that the expression of NQO1 was markedly down-regulated, Toll-like receptor 4 (TLR4) and TGF-β1 upregulated in vivo and in vitro under diabetic conditions. Overexpression of NQO1 suppressed pro-inflammatory cytokines secretion (IL-6, TNF-α, MCP-1), extracellular matrix (ECM) accumulation (collagen Ⅳ, Fibronectin) and epithelial-mesenchymal transition (EMT) (α-SMA, E-cadherin) in db/db mice kidney and high glucose cultured human renal tubular cells (HK-2). Furthermore, NQO1 overexpression ameliorated high glucose-induced TLR4/NF-κB and TGF-β/Smad pathway activation. Mechanistic studies demonstrated that TLR4 inhibitor (TAK-242) suppressed TLR4/NF-κB signaling pathway, pro-inflammatory cytokines secretion, EMT and ECM-related protein expression in HG-exposed HK-2 cells. In addition, we found that antioxidants NAC and tempol increased the expression of NQO1, decreased the expression of TLR4, TGF-β1, Nox1, Nox4 and ROS production in HK-2 cells cultured with high glucose. Conclusions: These above data suggest that NQO1 alleviates diabetes-induced renal inflammation and fibrosis by regulating TLR4/NF-κB and TGF-β/Smad signaling pathways.

scholarly journals YKL-40 Aggravates Early-Stage Atherosclerosis by Inhibiting Macrophage Apoptosis in an Aven-dependent Way

2021 ◽  
Vol 9 ◽  
Author(s):  
Wei Huan ◽  
Liu Yandong ◽  
Wang Chao ◽  
Zou Sili ◽  
Bai Jun ◽  
...  
Keyword(s):  
Early Stage ◽  
Expression Level ◽  
Atherosclerotic Plaques ◽  
Caspase 9 ◽  
Apoptosis Rate ◽  
Macrophage Apoptosis ◽  
Apoptosis Inhibitor ◽  
Human Carotid

Objective: programmed cell removal in atherosclerotic plaques plays a crucial role in retarding lesion progression. Macrophage apoptosis has a critical role in PrCR, especially in early-stage lesions. YKL-40 has been shown to be elevated as lesions develop and is closely related to macrophages. This study aimed to determine the effect of YKL-40 on regulating macrophage apoptosis and early-stage atherosclerosis progression.Research design and Methods: The correlations among the expression level of YKL-40, the area of early-stage plaque, and the macrophage apoptosis rate in plaques have been shown in human carotid atherosclerotic plaques through pathological and molecular biological detection. These results were successively confirmed in vivo (Ldlr−/- mice treated by YKL-40 recombinant protein/neutralizing antibody) and in vitro (macrophages that Ykl40 up-/down-expressed) experiments. The downstream targets were predicted by iTRAQ analysis.Results: In early-stage human carotid plaques and murine plaques, the YKL-40 expression level had a significant positive correlation with the area of the lesion and a significant negative correlation with the macrophage apoptosis rate. In vivo, the plaque area of aortic roots was significantly larger in the recomb-YKL-40 group than that in IgG group (p = 0.0247) and was significantly smaller in the anti-YKL-40 group than in the IgG group (p = 0.0067); the macrophage apoptosis rate of the plaque in aortic roots was significantly lower in the recomb-YKL-40 group than that in IgG group (p = 0.0018) and was higher in anti-YKL-40 group than that in VC group. In vitro, the activation level of caspase-9 was significantly lower in RAW264.7 with Ykl40 overexpressed than that in controls (p = 0.0054), while the expression level of Aven was significantly higher than that in controls (p = 0.0031). The apoptosis rate of RAW264.7 treated by recomb-YKL40 was significantly higher in the Aven down-regulated group than that in the control group (p < 0.001). The apoptosis inhibitor Aven was confirmed as the target molecule of YKL-40. Mechanistically, YKL-40 could inhibit macrophage apoptosis by upregulating Aven to suppress the activation of caspase-9.Conclusion: YKL-40 inhibits macrophage apoptosis by upregulating the apoptosis inhibitor Aven to suppress the activation of caspase-9, which may impede normal PrCR and promote substantial accumulation in early-stage plaques, thereby leading to the progression of atherosclerosis.

LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma

2020 ◽  
Vol 98 (5) ◽  
pp. 556-564
Author(s):  
Jubo Wang ◽  
Yu Quan ◽  
Jian Lv ◽  
Quan Dong ◽  
Shouping Gong
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Protein Expression ◽  
Caspase 9 ◽  
Isocitrate Dehydrogenase 1 ◽  
Genetic Changes ◽  
Primary Glioblastoma ◽  
U251 Cells

Glioma is a type of brain tumor that is common globally, and is associated with a variety of genetic changes. It has been reported that isocitrate dehydrogenase 1 (IDH1) is overexpressed in glioma and in HeLa cells. The lncRNA IDH1-AS1 is believed to interact with IDH1, and when IDH1-AS1 is overexpressed, HeLa cell proliferation is inhibited. However, the effects of IDH1-AS1 on glioma were relatively unknown. The results from this work show that IDH1-AS1 is downregulated in the glioma tissues. We used primary glioblastoma cell lines U251 and U87-MG to study the effects of IDH1-AS1 on glioma cell growth, in vitro and in vivo. We found that when IDH1-AS1 is overexpressed cell proliferation is inhibited, cell cycle is arrested at the G1 phase, and the protein expression levels of cyclinD1, cyclinA, cyclinE, CDK2, and CDK4 are decreased. We found that cell apoptosis was increased when IDH1-AS1 was overexpressed, as evidenced by increases in the levels of cleaved caspase-9 and -3. Conversely, knockdown of IDH1-AS1 promoted cell proliferation. Moreover, we proved that overexpression of IDH1-AS1 inhibits the tumorigenesis of U251 cells, in vivo. Furthermore, IDH1-AS1 did not affect IDH1 protein expression, but altered its enzymatic activities in glioma cells. Silencing of IDH1 reversed the effects of IDH1-AS1 upregulation on cell viability. Hence, our study provides first-hand evidence for the effects of lncRNA IDH1-AS1 on gliomas. Because overexpressing IDH1-AS1 inhibited cell growth, IDH1-AS1 could also be considered as a potential target for glioma treatment.

scholarly journals Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes

2015 ◽  
Vol 308 (5) ◽  
pp. C362-C371 ◽  
Author(s):  
Konstantinos A. Papadakis ◽  
James Krempski ◽  
Jesse Reiter ◽  
Phyllis Svingen ◽  
Yuning Xiong ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Effector Memory ◽  
Antiviral Immune Response ◽  
Ifn Γ ◽  
Tgf Β1

KLF10 has recently elicited significant attention as a transcriptional regulator of transforming growth factor-β1 (TGF-β1) signaling in CD4+ T cells. In the current study, we demonstrate a novel role for KLF10 in the regulation of TGF-β receptor II (TGF-βRII) expression with functional relevance in antiviral immune response. Specifically, we show that KLF10-deficient mice have an increased number of effector/memory CD8+ T cells, display higher levels of the T helper type 1 cell-associated transcription factor T-bet, and produce more IFN-γ following in vitro stimulation. In addition, KLF10−/− CD8+ T cells show enhanced proliferation in vitro and homeostatic proliferation in vivo. Freshly isolated CD8+ T cells from the spleen of adult mice express lower levels of surface TGF-βRII (TβRII). Congruently, in vitro activation of KLF10-deficient CD8+ T cells upregulate TGF-βRII to a lesser extent compared with wild-type (WT) CD8+ T cells, which results in attenuated Smad2 phosphorylation following TGF-β1 stimulation compared with WT CD8+ T cells. Moreover, we demonstrate that KLF10 directly binds to the TGF-βRII promoter in T cells, leading to enhanced gene expression. In vivo viral infection with Daniel's strain Theiler's murine encephalomyelitis virus (TMEV) also led to lower expression of TGF-βRII among viral-specific KLF10−/− CD8+ T cells and a higher percentage of IFN-γ-producing CD8+ T cells in the spleen. Collectively, our data reveal a critical role for KLF10 in the transcriptional activation of TGF-βRII in CD8+ T cells. Thus, KLF10 regulation of TGF-βRII in this cell subset may likely play a critical role in viral and tumor immune responses for which the integrity of the TGF-β1/TGF-βRII signaling pathway is crucial.

scholarly journals In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shintaro Mukohara ◽  
Yutaka Mifune ◽  
Atsuyuki Inui ◽  
Hanako Nishimoto ◽  
Takashi Kurosawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Achilles Tendon ◽  
Mrna Expression ◽  
High Glucose ◽  
Control Group ◽  
Type I

Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

Sign in / Sign up

Export Citation Format

Share Document