scholarly journals Niaoduqing Granules Inhibits TGF-β1-induced Epithelial-Mesenchymal Transition in Human Renal Tubular Epithelial HK-2 Cells

2020 ◽  
Author(s):  
Chu-Ying Huo ◽  
Hua-Yi Yang ◽  
Wei-Min Ning ◽  
Lin-Zhong Yu ◽  
Chun-Lin Fan ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Morphological Changes ◽  
Migration And Invasion ◽  
Type I ◽  
Mesenchymal Transition ◽  
Public Health Burden ◽  
Fluorescence Confocal Microscopy ◽  
Renal Tubular ◽  
Tgf Β1

Abstract Background: Chronic renal failure (CRF) is a worldwide public health burden. Niaoduqing granules (NDQ) is widely used for CRF treatment in China. However, the underlying mechanism of NDQ is not fully studied. This study is aimed to investigate whether NDQ ameliorate CRF by inhibiting TGF-β1-induced EMT in human renal tubular epithelial HK-2 cells.Methods: MTT assay and colony formation assay were used to investigate the cytotoxicity of NDQ in HK-2 cells. Morphological changes of HK-2 cells after TGF-β1 or/and NDQ treatment were observed under a microscope. Wound-healing, migration and invasion assays were performed to determine the cell movement, migratory and invasive abilities, respectively. Western blot analysis was carried out to examine the protein levels of TGF-β type I receptor (TβRI) and EMT-associated factors. Fluorescence confocal microscopy was applied to observe the organization of F-actin.Results: NDQ suppressed TβRI expression dose-dependently. NDQ inhibited TGF-β1-stimulated EMT in HK-2 cells, supported by the evidences that NDQ prevented morphology change, attenuated cell migration and invasion, downregulated EMT factors and reorganized F-actin distribution in TGF-β1-stimulated HK-2 cells.Conclusions: NDQ attenuates chronic renal failure which may be associated with inhibition of TβRI expression and EMT process.

scholarly journals Adhesion to type I collagen fibrous gels induces E- to N-cadherin switching without other EMT-related phenotypes in lung carcinoma cell A549

2020 ◽  
Author(s):  
Hitomi Fujisaki ◽  
Sugiko Futaki ◽  
Masashi Yamada ◽  
Kiyotoshi Sekiguchi ◽  
Toshihiko Hayashi ◽  
...  
Keyword(s):  
Single Cell ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Type I ◽  
Mesenchymal Transition ◽  
Cell Behaviors ◽  
Tgf Β1 ◽  
Cells Cultured ◽  
Cell Cell

AbstractIn culture system, environmental factors, such as increasing exogenous growth factors and adhesion to type I collagen (Col-I) induce epithelial-to-mesenchymal transition (EMT) in cells. Col-I molecules maintain a non-fibril form under acidic conditions, and they reassemble into fibrils under physiological conditions. Col-I fibrils often assemble to form three-dimensional gels. The gels and non-gel-form of Col-I can be utilized as culture substrates and different gel-forming state often elicit different cell behaviors. However, gel-form dependent effects on cell behaviors, including EMT induction, remain unclear. EMT induction in lung cancer cell line A549 has been reported via adhesion to Col-I but the effects of gel form dependency are unelucidated. This study investigated the changes in EMT-related behaviors in A549 cells cultured on Col-I gels.We examined cell morphology, proliferation, single-cell migration and expression of EMT-related features in A549 cells cultured on gels or non-gel form of Col-I and non-treated dish with or without transforming growth factor (TGF)-β1. On Col-I gels, some cells kept cell–cell contacts and formed clusters, others maintained single-cell form. In cell–cell contact regions, E-cadherin expression was downregulated, whereas that of N-cadherin was upregulated. Vimentin and integrins α2 and β1 expression were not increased. In TGF-β1-treated A549 cells, cadherin switched from E- to N-cadherin. Their morphology changed to a mesenchymal form and cells scattered with no cluster formation. Vimentin, integrins α2 and β1 expression were upregulated. Thus, we concluded that culture on Col-I fibrous gels induced E- to N-cadherin switching without other EMT-related phenotypes in A549 cells.

Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

2019 ◽  
Author(s):  
Zongli Ding ◽  
Wenwen Du ◽  
Zhe Lei ◽  
Yang Zhang ◽  
Jianjie Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wound Healing ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Wound Healing Assay ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background: TGF-β1 signaling is a potent inducer of epithelial-mesenchymal transition (EMT) in various cancers. Our previous study has indicated that NRP1 was significantly up-regulated and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the function of NRP1 in regulation of TGF-β1-induced EMT and NSCLC cell migration and invasion remained unclear. Methods: The differential expression level of NRP1 was determined by RT-PCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine cell ability of migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanism. Results: Increased expression of NRP1 was found in metastatic NSCLC tissues and can promote NSCLC metastasis in vivo. Transwell assays, wound healing assay and western blot analysis showed that knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of A549 and H226 cells. Furthermore, overexpression of NRP1 could weak the decreased migratory and invasive capabilities with SIS3 treatment. Co-IP data showed that NRP1 can interact with TGFβRⅡ to induce EMT. Conclusion: This is the first time to report that NRP1 can modulate TGF-β1-induced EMT and cell migration and invasion in NSCLC.

C-terminal Propeptide of Type-I Procollagen as a Possible Biochemical Marker for Preclinical Detection of Cardiac Disease in Chronic Renal Failure

2007 ◽  
Vol 7 (5) ◽  
pp. 804-809
Author(s):  
Azza Mohamed Omar Ab Rahmant ◽  
Sally Ahmed Farid El . ◽  
Ihab Zaki El-Hakim . ◽  
Maha Amin Rasheed .
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Cardiac Disease ◽  
Biochemical Marker ◽  
Type I ◽  
Type I Procollagen

Morphological Changes in the Aorta of Rabbits with Chronic Renal Failure

1983 ◽  
Vol 17 (1) ◽  
pp. 119-125 ◽  
Author(s):  
E. Tvedegaard ◽  
O. Kamstrup ◽  
M. Nielsen ◽  
H. Klem Thomsen
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Morphological Changes

FGF-1 reverts epithelial-mesenchymal transition induced by TGF-β1 through MAPK/ERK kinase pathway

2010 ◽  
Vol 299 (2) ◽  
pp. L222-L231 ◽  
Author(s):  
Carlos Ramos ◽  
Carina Becerril ◽  
Martha Montaño ◽  
Carolina García-De-Alba ◽  
Remedios Ramírez ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Smooth Muscle Actin ◽  
Substantial Reduction ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Opposite Process ◽  
Kinase Pathway ◽  
Tgf Β1 ◽  
Erk Kinase

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the expansion of the fibroblast/myofibroblast population and aberrant remodeling. However, the origin of mesenchymal cells in this disorder is still under debate. Recent evidence indicates that epithelial-mesenchymal transition (EMT) induced primarily by TGF-β1 plays an important role; however, studies regarding the opposite process, mesenchymal-epithelial transition, are scanty. We have previously shown that fibroblast growth factor-1 (FGF-1) inhibits several profibrogenic effects of TGF-β1. In this study, we examined the effects of FGF-1 on TGF-β1-induced EMT. A549 and RLE-6TN (human and rat) alveolar epithelial-like cell lines were stimulated with TGF-β1 for 72 h, and then, in the presence of TGF-β1, were cultured with FGF-1 plus heparin for an additional 48 h. After TGF-β1 treatment, epithelial cells acquired a spindle-like mesenchymal phenotype with a substantial reduction of E-cadherin and cytokeratins and concurrent induction of α-smooth muscle actin measured by real-time PCR, Western blotting, and immunocytochemistry. FGF-1 plus heparin reversed these morphological changes and returned the epithelial and mesenchymal markers to control levels. Signaling pathways analyzed by selective pharmacological inhibitors showed that TGF-β1 induces EMT through Smad pathway, while reversion by FGF-1 occurs through MAPK/ERK kinase pathway, resulting in ERK-1 phosphorylation and Smad2 dephosphorylation. These findings indicate that TGF-β1-induced EMT is reversed by FGF-1 and suggest therapeutic approaches to target this process in IPF.

Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells

2011 ◽  
Vol 300 (4) ◽  
pp. F1017-F1025 ◽  
Author(s):  
Hongli Lin ◽  
Dapeng Wang ◽  
Taihua Wu ◽  
Cui Dong ◽  
Nan Shen ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Cell Model ◽  
Mesenchymal Transition ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Core Fucosylation ◽  
Tgf Β1

Posttranslational modification of proteins could regulate their multiple biological functions. Transforming growth factor-β receptor I and II (ALK5 and TGF-βRII), which are glycoproteins, play important roles in the renal tubular epithelial-mesenchymal transition (EMT). In the present study, we examined the role of core fucosylation of TGF-βRII and ALK5, which is regulated by α-1,6 fucosyltransferase (Fut8), in the process of EMT of cultured human renal proximal tubular epithelial (HK-2) cells. The typical cell model of EMT induced by TGF-β1 was constructed to address the role of core fucosylation in EMT. Core fucosylation was found to be essential for both TGF-βRII and ALK5 to fulfill their functions, and blocking it with Fut8 small interfering RNA greatly reduced the phosphorylation of Smad2/3 protein, caused the inactivation of TGF-β/Smad2/3 signaling, and resulted in remission of EMT. More importantly, even with high levels of expressions of TGF-β1, TGF-βRII, and ALK5, blocking core fucosylation also could attenuate the EMT of HK-2 cells. Thus blocking core fucosylation of TGF-βRII and ALK5 may attenuate EMT independently of the expression of these proteins. This study may provide new insight into the role of glycosylation in renal interstitial fibrosis. Furthermore, core fucosylation may be a novel potential therapeutic target for treatment of renal tubular EMT.

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