scholarly journals Silencing Herg1 by shRNA inhibits the proliferation and invasion of osteosarcoma in vivo and in vitro

2021 ◽  
Author(s):  
Zhida Chen ◽  
Chao Song ◽  
Yunping Chen ◽  
Lili Xiao ◽  
Yuanjie Jiang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Nuclear Translocation ◽  
Affinity Purification ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Nude Mouse Model ◽  
Proliferation And Invasion

Abstract Background: Osteosarcoma is the most common malignant bone tumor of childhood, and improvements in the survival rates have reached a plateau phase. This study was aimed to explore the the importance of the human ether-a-go-go-related potassium channel (Herg1) in the proliferation and invasion of osteosarcoma.Methods: The effects of Herg1 silenced on osteosarcoma cell proliferation and invasion were detected by were detected by CCK-8 assay, wound healing assay and transwell assay, respectively. Tandem affinity purification, mass spectrometry and Dual luciferase reporter assay were used to find out possible molecules responsible for the action of Herg1 on osteosarcoma cells. Nude mouse model was used to investigate the in vivo functions of Herg1. Results: Herg1 silencing by shRNA significantly suppressed the proliferation and invasion of osteosarcoma cells in vitro as well as tumorigenicity and metastasis in nude mice. Moreover, Herg1 promoted osteosarcoma progression via turning off Hippo signaling pathway, leading to the activation of Yes-associated protein (YAP). Mechanistically, Herg1 co-localized and interacted with NF2 (also called Merlin), and this interaction probably caused the de-phosphorylation of MST1/2 and LATS1/2, which drove YAP nuclear translocation and transcriptional activation. Conclusion: Herg1 acts as an oncogene in osteosarcoma and may therefore serve as a useful therapeutic target for osteosarcoma patients.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells

2016 ◽  
Vol 24 (5) ◽  
pp. 381-389 ◽  
Author(s):  
Feng Jiang ◽  
Yan Shi ◽  
Hong Lu ◽  
Guojun Li
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Mesenchymal Transition ◽  
Armadillo Repeat ◽  
Proliferation And Invasion

Armadillo repeat-containing protein 8 (ARMC8) plays an important role in regulating cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. However, the expression pattern and role of ARMC8 in osteosarcoma are still unclear. In this study, our aims were to examine the effects of ARMC8 on osteosarcoma and to explore its underlying mechanism. Our results demonstrated that ARMC8 was overexpressed in osteosarcoma cell lines. Knockdown of ARMC8 significantly inhibited osteosarcoma cell proliferation in vitro and markedly inhibited xenograft tumor growth in vivo. ARMC8 silencing also suppressed the epithelial‐mesenchymal transition (EMT) phenotype, as well as inhibited the migration and invasion of osteosarcoma cells. Furthermore, knockdown of ARMC8 obviously inhibited the expression of β-catenin, c-Myc, and cyclin D1 in MG-63 cells. In conclusion, this report demonstrates that ARMC8 silencing inhibits proliferation and invasion of osteosarcoma cells. Therefore, ARMC8 may play an important role in the development and progression of human osteosarcoma and may represent a novel therapeutic target in the treatment of osteosarcoma.

scholarly journals Inhibitory Effects of Targeted Regulatory LKB1 Gene on the Proliferation and Invasion of Osteosarcoma Cells

2021 ◽  
Vol 21 (01) ◽  
Author(s):  
Jie Liu
Keyword(s):  
Transcription Factor ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Regulatory Genes ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Inhibitory Effects ◽  
Proliferation And Invasion

In this study, Immunodeficiency Nude Mouse Osteosarcoma Xenograft Model was subjected to the drug intervention to explore the effect of bexarotene on the proliferation and invasion of osteosarcoma cell lines in vitro. The inhibitory effects of targeted regulatory genes on the proliferation and invasion of osteosarcoma cells were studied through various in vitro experiments include bioinformatics combined with tissue microarray research, transcription factor prediction combined with co-expression analysis to predict the transcription factor of targeted regulatory genes in osteosarcoma. The RXR protein family, LKB1, AMPK pathway, and mTOR are closely related to the body’s immune regulation. The oral administration of Bexarotene could inhibit the proliferation and able to up-regulate the expression of LKB1 gene in living osteosarcoma tissue. The xenograft model of immunodeficiency nude mice used in this study was reason for reduced the potential immunoregulatory effect of drug targeted LKB1 therapy to a certain extent. However, overexpression of LKB1 in vivo, and combined immunotherapy may become an important immunotherapy approach for osteosarcoma. LKB1 targeted therapy can potentially be used as one of the alternative treatments for mTOR inhibitors.

scholarly journals LncRNA GAS5 Suppresses the Proliferation and Invasion of Osteosarcoma Cells via the miR-23a-3p/PTEN/PI3K/AKT Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972095309
Author(s):  
Jianmin Liu ◽  
Ming Chen ◽  
Longyang Ma ◽  
Xingbo Dang ◽  
Gongliang Du
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Luciferase Reporter Gene ◽  
Nude Mouse Model ◽  
Cell Functions ◽  
Proliferation And Invasion

Accumulating evidence has shown that long noncoding RNA GAS5 is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is still largely unclear. In this study, we found that GAS5 was downregulated in human osteosarcoma tissues and cell lines compared with matched adjacent tissues and normal osteoblast cells. Overexpression of GAS5 could significantly suppress the growth and invasion of osteosarcoma cells, while downregulation of GAS5 promoted cell proliferation and invasion. We confirmed that GAS5 could directly bind with miR-23a-3p by using luciferase reporter gene and RNA immunoprecipitation and pull-down assay. Downregulation of miR-23a-3p repressed cell proliferation and invasion. Overexpression of miR-23a-3p counterbalanced the inhibition effect of GAS5 on cell proliferation and invasion. Further studies indicated that overexpression of GAS5 inhibited cell proliferation and metastasis by regulating phosphatase and tensin homolog (PTEN). PTEN was authenticated as a target of miR-23a-3p. Upregulation of GAS5 or silence of miR-23a-3p increased the level of PTEN, while downregulation of GAS5 or overexpression of miR-23a-3p suppressed the expression of PTEN. In addition, overexpression of GAS5 could neutralize the effect of downregulating PTEN on osteosarcoma cell functions. We proved that GAS5 regulated the viability and invasion of osteosarcoma cells through the PI3K/AKT pathway. Moreover, overexpression of GAS5 could inhibit tumor growth in a xenograft nude mouse model in vivo. In summary, GAS5 functions as a competing endogenous RNA, sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals p53 upregulated by HIF-1α promotes hypoxia-induced G2/M arrest and renal fibrosis in vitro and in vivo

2018 ◽  
Vol 11 (5) ◽  
pp. 371-382 ◽  
Author(s):  
Limin Liu ◽  
Peng Zhang ◽  
Ming Bai ◽  
Lijie He ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Renal Fibrosis ◽  
Intraperitoneal Administration ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
P53 Expression ◽  
Tubular Cells

Abstract Hypoxia plays an important role in the genesis and progression of renal fibrosis. The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-1α on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins B1 and D1, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α (2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-1α-binding site. The HIF-1α–HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-1α suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis.

scholarly journals Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2019 ◽  
Author(s):  
Joerg Fellenberg ◽  
Burkhard Lehner ◽  
Heiner Saehr ◽  
Astrid Schenker ◽  
Pierre Kunz
Keyword(s):  
Tumor Suppressor ◽  
Therapeutic Strategies ◽  
High Dose ◽  
Osteosarcoma Cell ◽  
Tumor Suppressor Function ◽  
Osteosarcoma Cells ◽  
Aberrant Expression ◽  
Suppressor Function

Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.

scholarly journals CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuxiang Lin ◽  
Jie Zhang ◽  
Yan Li ◽  
Wenhui Guo ◽  
Lili Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Triple Negative Breast Cancer ◽  
Transcriptional Activation ◽  
Triple Negative ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Luciferase Reporter

Abstract Background Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. Methods The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. Results CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. Conclusion Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

2020 ◽  
Author(s):  
Jianmin Liu ◽  
Ming Chen ◽  
Longyang Ma ◽  
Xingbo Dang ◽  
Gongliang Du
Keyword(s):  
Tumor Suppressor ◽  
Tumor Growth ◽  
Akt Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Cell Behaviors ◽  
Human Osteosarcoma ◽  
Proliferation And Invasion

Abstract Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and non-malignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and downregulated miR-23a-3p that post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo . Conclusion: GAS5 functions as a competing endogenous RNA , sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

scholarly journals MO069HIF-1Α C-TERMINAL TRANSCRIPTIONAL ACTIVATION DOMAIN MEDIATED KLF5 SIGNALING DRIVES AKI TO CKD PROGRESSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Zuolin Li ◽  
Jia-ling Ji ◽  
Linli Lv ◽  
Yan Yang ◽  
Tao-tao Tang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Ischemic Injury ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Mice Model ◽  
Ckd Progression ◽  
Transcriptional Activation Domain ◽  
Tubular Cells

Abstract Background and Aims Acute kidney injury (AKI) is increasingly recognized as a major risk factor for progression to CKD. However, the mechanisms governing AKI to CKD progression are poorly understood. Hypoxia is a key player in the pathophysiology of the AKI to CKD transition. Thus, we aimed to investigate the exact mechanisms of AKI to CKD progression mediated by hypoxia. Method Mild ischemic injury and severe ischemic injury (AKI-to-CKD transition) were established by clamping renal pedicle for 30 and 40 minutes, respectively. Meanwhile, the mice model of AKI-to-CKD transition was treated with HIF-1α inhibitor, PX-478. In vitro, PHD inhibition and combined PHD with FIH inhibition mimic the HIF-1α activation caused by mild or severe hypoxia, respectively. Besides the human proximal tubular epithelial cell line HK-2, tubular cells were isolated from mice for primary culture. KLF5 knockdown, FIH and HIF-1α C-terminal transcriptional activation domain (C-TAD) overexpression in tubular cells were achieved by Lentiviral transfection. Immunocoprecipitation was used to explore the relationship between the HIF-1α and FIH-1. Luciferase reporter assay was used to investigate whether KLF5 was regulated transcriptionally by HIF-1α C-TAD. To explore the roles of FIH-1 and HIF-1α C-TAD in vivo, FIH-1 and HIF-1α C-TAD overexpression (Lentivirus-mediated) was given after severe ischemic injury or mild ischemic injury via tail vein injection, respectively. Results AKI to CKD progression was highly associated with the time-course expression of tubular HIF-1α in severe ischemia/reperfusion injury. Interestingly, ameliorated AKI-to-CKD transition was observed by treating PX-478, which destabilized HIF-1α. In vitro, fibrogenesis could be induced by combined PHD with FIH inhibitor treatment in TEC. More interestingly, alleviated fibrogenesis could be achieved by knockdown of KLF5 and overexpression of FIH, respectively, while HIF-1α C-TAD overexpression promoted fibrogenesis in tubular cells. Immunocoprecipitation results indicated that HIF-1α and FIH-1 are interactive. Furthermore, we demonstrated that KLF5 could be regulated transcriptionally by HIF-1α C-TAD by luciferase reporter assay. In vivo, AKI to CKD progression was ameliorated significantly when mice model of AKI-to-CKD transition intervened with FIH-1 overexpression (Lentivirus-mediated). However, treatment of HIF-1α C-TAD (Lentivirus-mediated) in mild ischemic injury model could promote progression of CKD significantly. Conclusion FIH-1 mediated HIF-1α C-TAD activation was the key mechanism of AKI to CKD transition by transcriptionally regulating the KLF5 pathway in tubules. Blockade of FIH-1 mediated HIF-1α C-TAD in tubules may serve as a novel therapeutic approach to ameliorate AKI to CKD progression.

Sign in / Sign up

Export Citation Format

Share Document