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Rna renal fibrosis

Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
Alternative splicing is a fundamental phenomenon to build protein diversity in health and diseases. Extra Domain A+ Fibronectin (EDA+Fn) is an alternatively spliced form of fibronectin protein present in the extra cellular matrix (ECM) in renal fibrosis. Podocytes are spectacular cell type and play a key role in filtration and synthesise ECM proteins in renal physiology and pathology. TGFβ1 is a strong stimulator of ECM proteins in renal injury. In this study, we have investigated alternative splicing of EDA+ Fn in human podocytes in response to TGFβ1...
February 28, 2018: Cellular and Molecular Biology
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Tubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks...
February 28, 2018: Scientific Reports
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
Malte Kölling, Celina Genschel, Tamas Kaucsar, Anika Hübner, Song Rong, Roland Schmitt, Inga Sörensen-Zender, George Haddad, Andreas Kistler, Harald Seeger, Jan T Kielstein, Danilo Fliser, Hermann Haller, Rudolf Wüthrich, Martin Zörnig, Thomas Thum, Johan Lorenzen
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells...
February 21, 2018: Scientific Reports
Kyung Mok Kim, Ki Wung Chung, Hyeong Oh Jeong, Bonggi Lee, Dae Hyun Kim, June Whoun Park, Seong Min Kim, Byung Pal Yu, Hae Young Chung
Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI)...
January 19, 2018: Oncotarget
Meng Xue, Yang Li, Fang Hu, Yi-Jie Jia, Zong-Ji Zheng, Ling Wang, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells...
January 22, 2018: Biochemical and Biophysical Research Communications
S-G Zhou, W Zhang, H-J Ma, Z-Y Guo, Y Xu
OBJECTIVE: To examine the role of long non-coding ribonucleic acid (LncRNA) TCONS_00088786 in the development of renal interstitial fibrosis and its potential mechanism in this process. MATERIALS AND METHODS: Unilateral ureteral obstruction (UUO) was used to induce tubulointerstitial fibrosis. Masson staining showed the degree of renal fibrosis in UUO mice. Immunohistochemistry and immunofluorescence were performed to detect the fibrosis-related proteins, the 24-h urine volume and protein content...
January 2018: European Review for Medical and Pharmacological Sciences
Chi Young Song, Nayaab S Khan, Francesca-Fang Liao, Bin Wang, Ji Soo Shin, Joseph V Bonventre, Kafait U Malik
Background: Recently we reported that angiotensin II (Ang II)-induced hypertension is mediated by group IV cytosolic phospholipase A2α (cPLA2α) via production of pro-hypertensive eicosanoids. Since Ang II increases blood pressure via its action in the subfornical organ (SFO), it led us to investigate the expression and possible contribution of cPLA2α to oxidative stress and development of hypertension in this brain area. Methods: Adenovirus (Ad)-green fluorescence protein (GFP) cPLA2α short hairpin (sh) RNA (Ad-cPLA2α shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad-enhanced cyan fluorescence protein cPLA2α DNA (Ad-cPLA2α DNA) and its control Ad-GFP DNA were transduced into SFO of cPLA2α+/+ and cPLA2α-/- male mice, respectively...
January 12, 2018: American Journal of Hypertension
Xing Zhao, Gang Luo, Yan Fan, Xiaoxue Ma, Jieqing Zhou, Hong Jiang
Renal interstitial fibrosis is the most common process by which chronic kidney diseases progress to end-stage renal failure. Epithelial-to-mesenchymal transitions (EMTs) play a crucial role in the progression of renal interstitial fibrosis. A newly identified cytokine, interleukin-like EMT inducer (ILEI), has been linked to EMT in some diseases. However, the effects of ILEI on renal tubular EMT have not yet been well established. Here, we characterize the expression of ILEI in tubular EMT and describe the role and mechanism of ILEI in transforming growth factor beta 1 (TGF-β1)-induced renal tubular EMT...
January 15, 2018: Cell Biochemistry and Function
Xiao-Yu Li, Shan-Shan Wang, Zhe Han, Fei Han, Yun-Peng Chang, Yang Yang, Mei Xue, Bei Sun, Li-Ming Chen
Fibrosis is the major pathological feature of diabetic kidney disease (DKD). Autophagy, a process to maintain metabolic homeostasis, is obviously inhibited in DKD. Triptolide (TP) is a traditional Chinese medicine extract known for immune suppression and anti-inflammatory and anti-cancer activities. In this study, we investigated the effects of TP on autophagy and fibrosis in DKD. TP restored autophagy and alleviated fibrosis in DKD rats and high-glucose-incubated human mesangial cells. After we applied 3-methyladenine (an autophagy inhibitor) and autophagy-related gene 5-small interfering RNA (siRNA), we found that the improvement of fibrosis on TP was related to the restoration of autophagy...
December 15, 2017: Molecular Therapy. Nucleic Acids
Si F Sun, Patrick Mk Tang, Min Feng, Xiao Jun, Xiao R Huang, Ping Li, Ronal Cw Ma, Hui Y Lan
TGF-β/Smad signaling plays an important role in diabetic nephropathy. The present study identified a novel Smad3-dependent long non-coding RNA (lncRNA) Erbb4-IR in the development of type-2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and was specifically induced by AGE via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN such as elevated microalbuminuria, serum creatinine and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs)...
December 8, 2017: Diabetes
Shuiling Zhao, Anindya Ghosh, Chao-Sheng Lo, Isabelle Chenier, James W Scholey, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined rat immortalized RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1-7) receptor (MasR) gene promoters...
February 1, 2018: Endocrinology
C Zhang, J Yuan, H Hu, W Chen, M Liu, J Zhang, S Sun, Z Guo
Kidney stone disease is a major cause of chronic renal insufficiency. The role of long non-coding RNAs (lncRNAs) in calcium oxalate-induced kidney damage is unclear. Therefore, we aimed to explore the roles of lncRNAs in glyoxylate-exposed and healthy mouse kidneys using microarray technology and bioinformatics analyses. A total 376 mouse lncRNAs were differentially expressed between the two groups. Using BLAST, 15 lncRNA homologs, including AU015836 and CHCHD4P4, were identified in mice and humans. The AU015836 expression in mice exposed to glyoxylate and the CHCHD4P4 expression in human proximal tubular epithelial (HK-2) cells exposed to calcium oxalate monohydrate were analyzed, and both lncRNAs were found to be upregulated in response to calcium oxalate...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Wenshan Lv, Fan Fan, Yangang Wang, Ezekiel Gonzalez-Fernandez, Chen Wang, Lili Yang, George W Booz, Richard J Roman
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD...
November 10, 2017: Physiological Genomics
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Wei Yang, Xuezhong Li, Shaopei Qi, Xueru Li, Kun Zhou, Suzhu Qing, Yong Zhang, Ming-Qing Gao
Increased levels of long noncoding RNA H19 (H19) have been observed in many inflammatory and organ fibrosis diseases including ulcerative colitis, osteoarthritis, liver fibrosis, renal fibrosis and pulmonary fibrosis. However, the role of H19 in bovine mastitis and mastitis-caused fibrosis is still unclear. In our study, H19 was characterized as a novel regulator of EMT induced by transforming growth factor-β1 (TGF-β1) in bovine mammary alveolar cell-T (MAC-T) cell line. We found that H19 was highly expressed in bovine mastitis tissues and inflammatory MAC-T cells induced by virulence factors of pathogens...
2017: PeerJ
Stefan Gauer, Yvonne Holzmann, Bettina Kränzlin, Sigrid C Hoffmann, Norbert Gretz, Ingeborg A Hauser, Margarete Goppelt-Struebe, Helmut Geiger, Nicholas Obermüller
Connective tissue growth factor (CTGF, also named CCN2) plays an important role in the development of tubulointerstitial fibrosis, which most critically determines the progression to end-stage renal failure in autosomal-dominant polycystic kidney disease (ADPKD), the most common genetically caused renal disease. We determined CTGF expression in a well-characterized animal model of human ADPKD, the PKD/Mhm (cy/+) rat. Kidneys of 12 weeks old (cy/+) as well as (+/+) non-affected rats were analyzed for CTGF RNA and protein expression by RT-PCR, Northern and Western blot analyses, in situ hybridization, and IHC...
December 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Patrick Ming-Kuen Tang, Shuang Zhou, Chun-Jie Li, Jinyue Liao, Jun Xiao, Qing-Ming Wang, Guang-Yu Lian, Jinhong Li, Xiao-Ru Huang, Ka-Fai To, Chi-Fai Ng, Charing Ching-Ning Chong, Ronald Ching-Wa Ma, Tin-Lap Lee, Hui-Yao Lan
Src activation has been associated with fibrogenesis after kidney injury. Macrophage-myofibroblast transition is a newly identified process to generate collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a TGF-β/Smad3-dependent manner. The potential role of the macrophage-myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying this by RNA sequencing at single-cell resolution, we uncovered a unique Src-centric regulatory gene network as a key underlying mechanism of macrophage-myofibroblast transition...
October 14, 2017: Kidney International
Jing Yan, Feng Du, Sheng-Dong Li, Ye Yuan, Jing-Yi Jiang, Si Li, Xin-Yu Li, Zhen-Xian Du
Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-β was significantly compromised...
October 3, 2017: Biochimica et Biophysica Acta
Bengu Tatar, Sukran Kose, Emel Pala, Erhan Tatar
BACKGROUND: The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. METHODS: Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group...
2017: Acta Medica (Hradec Králové)
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