scholarly journals P013 Potential Role of Epithelial Protein Disulphide Isomerases in Crohn’s Disease Fibrosis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S134-S135
Author(s):  
S Vieujean ◽  
S Hu ◽  
E Bequet ◽  
C Salée ◽  
C Massot ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Potential Role ◽  
In Vitro Experiments ◽  
Proteomic Study ◽  
Ht 29 ◽  
Tgf Β1 ◽  
Myofibroblastic Differentiation

Abstract Background Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. In in-vitro experiments, this myofibroblastic differentiation is elicited by a whole series of factors among which transforming growth factor-β1 (TGF-β1) seems to play a key role. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods We performed a pilot proteomic study comparing the proteome of surface epithelium isolated by laser-capture microdissection in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). The pro-fibrotic role of selected epithelial proteins was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2), Protein disulphide isomerase A6 (PDIA6) and Endoplasmic reticulum resident protein 44 (ERP44) which are 3 protein disulphide isomerases. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2, PDIA6, ERP44 as well as TGF-β1 intracellular expression and their secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin (Tm), led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. The application of blocking agents for AGR2, PDIA6, ERP44 or TGF-β1 in the supernatant of these Tm-pre-conditioned HT-29 cells, attenuated the myofibroblastic differentiation induced by this supernatant, suggesting a pro-fibrotic role of these secreted epithelial proteins. Conclusion The development of CD fibrotic strictures may involve ER stress in epithelial cells, releasing a whole set of proteins into their environment, including AGR2, PDIA6, ERP44 as well as TGF-β1, which could exercise a pro-fibrotic role through a paracrine action.

scholarly journals Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

2016 ◽  
Vol 310 (9) ◽  
pp. C755-C763 ◽  
Author(s):  
Mingfang Jiang ◽  
Qiang Yun ◽  
Feng Shi ◽  
Guangming Niu ◽  
Yang Gao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Target Genes ◽  
Binding Protein ◽  
Quantitative Polymerase Chain Reaction ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Stress Signaling

Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of microRNAs (miRNAs) in this process involved in PD remains poorly understood. Recent studies indicate that miR-384-5p plays an important role for cell survival in response to different insults, but the role of miR-384-5p in PD-associated neurotoxicity remains unknown. In this study, we investigated the role of miR-384-5p in an in vitro model of PD using dopaminergic SH-SY5Y cells treated with rotenone. We found that miR-384-5p was persistently induced by rotenone in neurons. Also, the inhibition of miR-384-5p significantly suppressed rotenone-induced neurotoxicity, while overexpression of miR-384-5p aggravated rotenone-induced neurotoxicity. Through bioinformatics and dual-luciferase reporter assay, miR-384-5p was found to directly target the 3′-untranslated region of glucose-regulated protein 78 (GRP78), the master regulator of ER stress sensors. Quantitative polymerase chain reaction and Western blotting analysis showed that miR-384-5p negatively regulated the expression of GRP78. Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress, which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1α). The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR-384-5p inhibitor. In contrast, overexpression of miR-384-5p enhanced ER stress signaling. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. Moreover, we observed a significant increase of miR-384-5p expression in primary neurons induced by rotenone. Taken together, our results suggest that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD.

Abstract 18708: Vascular Dysfunction in Hyperhomocysteinemia: In vitro Evidence for Endoplasmic Reticulum Stress-mediated Calcium-activated Potassium Channel Dysfunction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Wen-Tao Sun ◽  
Xiang-Chong Wang ◽  
Cheuk-Man Yu ◽  
Shun-Hay Pun ◽  
Qin Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Smooth Muscle ◽  
Cell Surface ◽  
Er Stress ◽  
Vascular Dysfunction ◽  
Cell Protein ◽  
Α Subunit ◽  
Whole Cell

Objectives: KCa channels play an important role in the control of vascular tone. Opening of IKCa and SKCa in endothelial cells underlies the classic EDHF pathway and promotes NO production. Smooth muscle BKCa provides a negative feedback mechanism opposing vasoconstriction and is an effector of NO and EDHF. Previous studies demonstrated homocysteine (Hcy), a risk factor for atherosclerosis, compromises NO and EDHF function, however, whether KCa is involved is poorly studied and the underlying mechanisms remain unknown. We studied the effect of Hcy on vascular KCa with the role of endoplasmic reticulum (ER) stress explored. Methods: In vitro studies were performed in porcine coronary arteries and primary cultured porcine coronary endothelial (PCECs) and smooth muscle cells (PCSMCs). IKCa and SKCa-, and BKCa-mediated relaxations were studied in endothelium-intact and -denuded arteries in a myograph. IKCa and SKCa currents in PCECs and BKCa current in PCSMCs were analyzed by whole-cell patch clamp and channel expressions were examined by western blot. Results: Hcy impairs the role of IKCa and SKCa, and BKCa in vasorelaxation. Relaxant responses to channel activators NS309 and NS1619 were attenuated and EDHF-type response was inhibited. Hcy suppressed IKCa and SKCa currents in PCECs and BKCa currents in PCSMCs. Inhibition of ER stress enhanced KCa currents and improved EDHF-type and channel activators-induced responses. Whole-cell protein levels of IKCa and SKCa remained unchanged in Hcy-exposed PCECs whereas IKCa and SKCa at cell surface were significantly decreased. Hcy lowered protein of β1 but not α subunit of BKCa in PCSMCs. The decrease in cell surface IKCa and SKCa and reduction of BKCa β1 were restored by ER stress inhibition. Further, inhibition of PERK increased BKCa β1 protein and enhanced BKCa current. Conclusion: ER stress mediates Hcy-induced vascular dysfunction through inhibition of KCa. Suppression of cell surface expression underlies ER stress-mediated IKCa and SKCa inhibition. Downregulation of BKCa β1 by PERK-ER stress pathway plays a key role in the loss of BKCa function. This study provides new mechanistic insights into the role of ER stress in vascular dysfunction. Supported by RGC GRF CUHK4774/12M & CUHK14118414, and NSFC 81200123.

scholarly journals Rapamycin Improves Palmitate-Induced ER Stress/NFκB Pathways Associated with Stimulating Autophagy in Adipocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jiajing Yin ◽  
Liping Gu ◽  
Yufan Wang ◽  
Nengguang Fan ◽  
Yuhang Ma ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Autophagy Flux ◽  
Protein Levels ◽  
Stress Effects ◽  
Stress Markers

Obesity-induced endoplasmic reticulum (ER) stress and inflammation lead to adipocytes dysfunction. Autophagy helps to adapt to cellular stress and involves in regulating innate inflammatory response. In present study, we examined the activity of rapamycin, a mTOR kinase inhibitor, against endoplasmic reticulum stress and inflammation in adipocytes. Anin vitromodel was used in which 3T3-L1 adipocytes were preloaded with palmitate (PA) to generate artificial hypertrophy mature adipocytes. Elevated autophagy flux and increased number of autophagosomes were observed in response to PA and rapamycin treatment. Rapamycin attenuated PA-induced PERK and IRE1-associated UPR pathways, evidenced by decreased protein levels of eIF2αphosphorylation, ATF4, CHOP, and JNK phosphorylation. Inhibiting autophagy with chloroquine (CQ) exacerbated these ER stress markers, indicating the role of autophagy in ameliorating ER stress. In addition, cotreatment of CQ abolished the anti-ER stress effects of rapamycin, which confirms the effect of rapamycin on ERs is autophagy-dependent. Furthermore, rapamycin decreased PA-induced nuclear translocation of NFκB P65 subunit, thereby NFκB-dependent inflammatory cytokines MCP-1 and IL-6 expression and secretion. In conclusion, rapamycin attenuated PA-induced ER stress/NFκB pathways to counterbalance adipocytes stress and inflammation. The beneficial of rapamycin in this context partly depends on autophagy. Stimulating autophagy may become a way to attenuate adipocytes dysfunction.

scholarly journals Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress

2017 ◽  
Vol 42 (4) ◽  
pp. 1313-1325 ◽  
Author(s):  
Ning Zhang ◽  
Wen-Ying Wei ◽  
Zheng Yang ◽  
Yan Che ◽  
Ya-Ge Jin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Er Stress ◽  
Disease Onset ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Aortic Banding

Background/Aims: An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Methods: Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/SH), sham+NOB (NOB/SH), AB+vehicle (VEH/AB), and AB+ NOB (NOB/AB). Animals (n = 15 per group) were treated with vehicle or NOB (50 mg/kg) for 4 weeks after disease onset. Results: NOB prevented cardiac hypertrophy induced by aortic banding (AB), as assessed by the cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers and cardiac function. In addition, NOB supplementation blunted the increased expression of NAPDH oxidase (NOX) 2 and NOX4 and mitigated endoplasmic reticulum (ER) stress and myocyte apoptosis in cardiac hypertrophy. Furthermore, NOB treatment attenuated the neonatal rat cardiomyocyte (NRCM) hypertrophic response stimulated by phenylephrine (PE) and alleviated ER stress. However, our data showed that NOB dramatically inhibited NOX2 expression but not NOX4 in vitro. Finally, we found that knockdown of NOX2 attenuated ER stress in NRCMs stimulated by PE. Conclusions: Inhibition of oxidative and ER stress by NOB in the myocardium may represent a potential therapy for cardiac hypertrophy. Moreover, there is a direct role of NOX2 in regulating ER stress stimulated by PE.

scholarly journals sFlt-1 commutes unfolded protein response into endoplasmic reticulum stress in trophoblast cells in preeclamptic pregnancies

2018 ◽  
Author(s):  
Sankat Mochan ◽  
Manoj Kumar Dhingra ◽  
Sunil Kumar Gupta ◽  
Shobhit saxena ◽  
Pallavi Arora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Late Onset ◽  
Trophoblast Cells ◽  
Bewo Cells ◽  
Placental Cells

AbstractPreeclampsia (PE) and its subtypes (early and late onset) are serious concerns all across the globe affecting about 8% of total pregnancies and accounts for approximately 60,000 deaths annually with a predominance in developing under-developed and countries. The two-stage model in the progression of this disease, deficient spiral artery remodelling and an imbalance between angiogenic (VEGF) and anti-antigenic factor(s) (sFlt-1) are well established facts pertaining to this disease. The presence of increased sFlt-1, high oxidative stress and Endoplasmic reticulum stress (ER stress) have been proposed in preeclamptic pregnancies. Recently, the role of endoplasmic reticulum stress in the onset of the variant forms of PE highlighted a new window to explore further. In our previous studies, we demonstrated that sFlt-1 can induce apoptosis and oxidative stress in trophoblast cells. However the role of sFlt-1, in inducing ER stress is not known so far. In the present study, we for the first time demonstrated significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to sera from preeclamptic pregnancies having increased concentration of sFlt-1. The expression of ER stress markers (GRP78, eIF2α, XBP1, ATF6 and CHOP) at both transcript and protein levels were compared (between preeclamptic and normotensive non-proteinuric women) at three different time points (8h, 14h and 24hrs), analyzed and found to be significant (p<0.05).ConclusionOur results suggested that sFlt-1, released from placental cells in preeclampsia may be one of the various factors having potential to induce endoplasmic reticulum stress in BeWo cells.

scholarly journals Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér
Keyword(s):  
Amino Acid ◽  
Zinc Finger ◽  
Cleavage Site ◽  
Potential Role ◽  
Binding Mode ◽  
Interaction Energies ◽  
Vitro Assay ◽  
Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

scholarly journals Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽  
2021 ◽  
Author(s):  
Yukina Takeichi ◽  
Takashi Miyazawa ◽  
Shohei Sakamoto ◽  
Yuki Hanada ◽  
Lixiang Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

c-Jun Inhibits Thapsigargin-Induced ER Stress Through Up-Regulation of DSCR1/Adapt78

2008 ◽  
Vol 233 (10) ◽  
pp. 1289-1300 ◽  
Author(s):  
Peng Zhao ◽  
Xiaoyan Xiao ◽  
Agnes S. Kim ◽  
M. Fatima Leite ◽  
Jinxia Xu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Wild Type Mouse ◽  
Mouse Fibroblast ◽  
Expression Levels ◽  
Mouse Fibroblasts ◽  
The Unfolded Protein Response ◽  
Calcineurin Activity

The endoplasmic reticulum (ER) is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed “ER stress”, can perturb ER function, leading to the activation of a complex response known as the unfolded protein response (UPR). Although c-Jun N-terminal kinase (JNK) activation is nearly always associated with cell death by various stimuli, the functional role of JNK in ER stress-induced cell death remains unclear. JNK regulates gene expression through the phosphorylation and activation of transcription factors, such as c-Jun. Here, we investigated the role of c-Jun in the regulation of ER stress-related genes. c-Jun expression levels determined the response of mouse fibroblasts to ER stress induced by thapsigargin (TG, an inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase). c-jun−/− mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts, while reconstitution of c-Jun expression in c-jun−/− cells (c-Jun Re) enhanced resistance to TG-induced cell death. The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-Jun Re than in c-jun−/− cells. Moreover, TG treatment significantly increased calcineurin activity in c-jun−/− cells, but not in c-Jun Re cells. In c-Jun Re cells, TG induced the expression of Adapt78, also known as the Down syndrome critical region 1 (DSCR1), which is known to block calcineurin activity. Taken together, our findings suggest that c-Jun, a transcription factor downstream of the JNK signaling pathway, up-regulates Adapt78 expression in response to TG-induced ER stress and contributes to protection against TG-induced cell death.

scholarly journals Identification of a microRNA signature in renal fibrosis: role of miR-21

2011 ◽  
Vol 301 (4) ◽  
pp. F793-F801 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Shanzhong Yang ◽  
Edward Abraham ◽  
Anupam Agarwal ◽  
Gang Liu
Keyword(s):  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Response To Treatment ◽  
Tubular Epithelial Cells ◽  
Altered Expression ◽  
Tnf Α ◽  
Tgf Β1

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.

Sign in / Sign up

Export Citation Format

Share Document