miR-133b and miR-199b knockdown attenuate TGF-β1-induced epithelial to mesenchymal transition and renal fibrosis by targeting SIRT1 in diabetic nephropathy

Sun, Zhiqiang; Ma, Yue; Chen, Fang; Wang, Shiying; Chen, Baoping; Shi, Jun

doi:10.1016/j.ejphar.2018.08.022

Cited by 95 publications

(87 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Understanding the interactions between miRNAs and lncRNAs to regulate genes involved in DN are important, as they will unravel the critical steps in DN progression. For example, in ECM accumulation (Figure 1), previous studies in DN mice showed that interactions of lncRNA CJ241444-miR-192 activates TGFB1/SMAD signaling (Kato et al, 2013) and lncRNA Erbb4-IR-miR-29b promotes the collagen genes expression, ECM accumulation and kidney injury (Sun et al, 2018b). In both of the studies (Kato et al, 2013;Sun et al, 2018a), the lncRNAs act as the miRNA sponge to exert the outcomes.…”

Section: Lncrna-mirna Interactions In Renal Hypertrophy and Ecm Accummentioning

confidence: 87%

“…Inhibition of NEAT1 expression in an animal model of DN causes a reduction of TGFB1, FN, and COL4A1 production (Huang et al, 2019). Similarly, lncRNA ERBB4-IR also promotes renal fibrosis via the activation of the TGFB/SMAD3 pathway (Zhou et al, 2014;Sun et al, 2018b). Interestingly, knockdown of this lncRNA ERBB4-IR in DN mice protected the mice from having high albuminuria and creatinine, as well as prevented renal fibrosis (Sun et al, 2018b).…”

Section: Long Noncoding Rnas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

“…Similarly, lncRNA ERBB4-IR also promotes renal fibrosis via the activation of the TGFB/SMAD3 pathway (Zhou et al, 2014;Sun et al, 2018b). Interestingly, knockdown of this lncRNA ERBB4-IR in DN mice protected the mice from having high albuminuria and creatinine, as well as prevented renal fibrosis (Sun et al, 2018b). Opposite to PVT-1 and NEAT-1, a hyperglycemic condition caused downregulation of lncRNA, CYP4B1-PS1-001 expression, which increases nucleolin (NCL) protein expression (Wang et al, 2016a;Wang et al, 2018b).…”

Section: Long Noncoding Rnas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

See 2 more Smart Citations

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

et al. 2020

View full text Add to dashboard Cite

Diabetic Nephropathy (DN) is the most common cause of End-stage renal disease (ESRD). Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden. Recent findings showed that noncoding RNAs (ncRNAs) play an important role in DN progression, potentially can be used as biomarkers and therapeutic targets. NcRNAs refers to the RNA species that do not encode for any protein, and the most known ncRNAs are the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Dysregulation of these ncRNAs was reported before in DN patients and animal models of DN. Importantly, there are some interactions between these ncRNAs to regulate the crucial steps in DN progression. Here, we aimed to discuss the reported ncRNAs in DN and their interactions with critical genes in DN progression. Elucidating these ncRNAs regulatory network will allow for a better understanding of the molecular mechanisms in DN and how they can act as new biomarkers for DN and also as the potential targets for treatment.

show abstract

Section: Lncrna-mirna Interactions In Renal Hypertrophy and Ecm Accummentioning

confidence: 87%

Section: Long Noncoding Rnas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

Section: Long Noncoding Rnas In Renal Hypertrophy and Ecm Accumulationmentioning

confidence: 99%

See 1 more Smart Citation

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is identi ed as a key factor in cancer development [17][18][19][20] and is also known to alleviate cardiac brosis in many animal models [8][9][10]. Lentiviral transfection of miR-133 was found to reduce renal interstitial brosis in old UUO mice [7] and renal brosis in diabetic rats [21]. In the present study, we induced the high expression of miR-133b in the kidney tissue through an intravenous injection of an miR-133b transfection complex.…”

Section: Discussionmentioning

confidence: 87%

“…On the other hand, the overexpression of miR-133a in primary murine hepatic stellate cells was shown to decrease the expression of collagen [22]. However, miR-133b was found to be overexpressed in TGF-β1treated HK-2 cells, and miR-133b inhibition attenuated the TGF-β1-induced EMT of HK-2 cells [21]. Our experiments con rmed the TGF-β1-mediated downregulation of miR-133 expression in a concentrationand time-dependent manner, and showed that the overexpression of miR-133b signi cantly inhibited the downregulation in the mRNA and protein expression of E-cadherin as well as the upregulation in the mRNA and protein levels of α-SMA, bronectin, Col3A1, and CTGF induced by TGF-β1.…”

Section: Discussionmentioning

confidence: 96%

Regulation of CTGF Expression by miR-133b for the Treatment of Renal Interstitial Fibrosis in Old UUO Rats

Cao

Wang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated the high expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) from old rats, which mediated the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.Methods: miR-133b expression induced during the EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and time points (0, 24, 48, and 72 h) was detected using real-time polymerase chain reaction. The target genes of miR-133b were validated using a dual-luciferase reporter assay. In vitro experiments were performed to observe mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-week-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. miR-133b、 target gene and other indexes mentioned above mRNA and protein levels and renal interstitial fibrosis were detected at 7 and 14 days.Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. Dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. miR-133b mimic transfection inhibited the TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidneys after injection of the miRNA-133b overexpression complex, significantly alleviating renal interstitial fibrosis in UUO mice.Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, consequently reducing the TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in old UUO mice.

show abstract

Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer

Gao

Wang

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

Background Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non‐small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC. Methods RNA and protein levels were detected by quantitative real‐time polymerase chain reaction (qRT–PCR) and western blotting assays. Cell proliferation was examined by cell counting kit‐8 (CCK‐8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR‐133b was verified by dual‐luciferase reporter assays. In vivo metastasis was monitored in the tail vein‐injected mice. Results FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial–mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor‐β (TGF‐β)/Smad signaling pathway. miR‐133b directly targeted the 3′‐UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo. Conclusions miR‐133b downregulates FOXL2 by targeting the 3′‐UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF‐β/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC.

show abstract

miR-133b and miR-199b knockdown attenuate TGF-β1-induced epithelial to mesenchymal transition and renal fibrosis by targeting SIRT1 in diabetic nephropathy

Cited by 95 publications

References 25 publications

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

Regulation of CTGF Expression by miR-133b for the Treatment of Renal Interstitial Fibrosis in Old UUO Rats

Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer

Contact Info

Product

Resources

About