Xiaoyan Bai

Transmembrane protein (TMEM) is a type of membrane proteins, encoded by TMEM gene, also known as integral membrane protein. TMEM gene family contains various members and its encoded proteins have various functions and expressed in numerous organs. It has been proved to be widely involved in the formation of a lot of organelle membranes, enzymes, receptors and channels, mediating numerous normal physiological functions and regulating various disease processes. At present, accumulating evidences at home and abroad have shown that TMEM is involved in regulating the occurrence and development of different tumors, cardiovascular and kidney diseases. The improved understanding of molecular mechanisms of TMEM genes and proteins may provide new directions and ideas for the prevention, diagnosis and treatment of diseases. In the present review, the roles of TMEM and biological functions in various cancers, cardiovascular and kidney diseases were discussed.

Purpose We aimed to conduct a retrospective analysis to assess the efficacy and safety of finerenone in patients with membranous nephropathy (MN). Methods This study conducted a retrospective analysis of patients with MN who were treated with finerenone for follow-up period ranging from 3 to 6 months. The study compared the estimated glomerular filtration rate (eGFR), urine total protein-to-creatinine ratio (PCR), urine albumin-to-creatinine ratio (ACR), serum creatinine concentration (SCr), blood pressure and serum potassium (K+) during the follow-up period. Result In this study, 20 patients with MN were treated with finerenone for a follow-up period of 3 to 6 months. Prior to treatment, the average eGFR was 65.15 mL/min/1.73 m², the average PCR was 3643.63 mg/g, and the average ACR was 2489.44 mg/g. After 3 months of treatment, 80% of patients experienced a decrease in PCR. The median decrease percentages in PCR and ACR are 24.49% and 28.82%, respectively. After 6 months of treatment, the median decrease percentages in PCR and ACR are 42.03% and 43.66%, respectively while the eGFR remained stable with little variation from baseline. During the treatment period, there were minimal changes in serum potassium levels and serum creatinine levels and no treatment discontinuations or hospitalizations due to hyperkalemia were observed. Blood pressure decreased by about 10 mmHg in 6 patients (30%), while there was no difference before and after the addition of finerenone in the remaining 14 (70%) patients. Conclusion The retrospective analysis indicates that finerenone treatment led to significant reductions in PCR and ACR in patients with membranous nephropathy over a 3 to 6-month period, with minimal impact on eGFR, SCr, and K+ levels, highlighting its capacity as a therapeutic option for MN patient group.

C57BL/6 mice are frequently utilized as murine models with the desired genetic background for altertion in multiple research contexts. So far, there is still a lack of comprehensive kidney morphology and single-cell transcriptome atlas at all stages of growth of C57BL/6 mice. To provide an interactive set of reference standards for the scientific community, we performed the current study to investigate the kidney’s development throughout the capillary-loop stage until senescence. Eight groups, with five to six mice each, represented embryonic stage (embryos 18.5 days), suckling period (1 day after birth), juvenile stage (1 month old), adulthood (containing 3 months old, 6 months old and 10 months old), reproductive senescence stage (20 months old), and post-senescence stage (30 months old), respectively. With age, the thickness of the glomerular basement membrane (GBM) was increased. Notably, GBM knobs appeared at three months and became frequent with age. Using single-cell transcriptome data, we evaluated how various biological process appear in particular cell types and investigated the potential mechanism of formation of GBM konbs. In conclusion, having access to detailed kidney morphology and single-cell transcriptome maps from C57BL/6 mice at various developmental stages of C57BL/6 mice would be a novel and major resource for biological research and testing of prospective therapeutic approaches.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-016-0382-3.

Aims: Altered activities of long non-coding RNAs (lncRNAs) have been implicated in the regulation of microRNAs. MicroRNA-27a (miR-27a) upregulation has been shown to induce endoplasmic reticulum stress (ER stress) and podocyte injury in diabetic nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of miR-27a with long intergenic non-coding RNA 1619 (LINC01619) and the target gene. Results: LINC01619 downregulation was found in human DN renal biopsy tissues and contributed to proteinuria and diminished renal function. LINC01619 was expressed in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619 exerted biological function by serving as a “sponge” for miR-27a, which negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In diabetic rats and high glucose cultured podocytes, LINC01619 triggered oxidative stress and podocyte injuries as demonstrated by increased apoptosis, diffuse podocyte foot process effacement and decreased renal function. Innovation and Conclusion: This study demonstrates that LINC01619 functions as a competing endogenous RNA (ceRNA) and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury in DN.

Correction to:Cell Death and Disease8, e2658 (2017); https://doi.org/10.1038/cddis.2017.74; published online 9 March 2017

Podocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin pathways have been involved in the pathogenesis of DN. Herein, we asked whether miR-27a mediates podocyte injury through PPARγ/β-catenin signaling in DN. The functional relevance of miR-27a, PPARγ and β-catenin were investigated in cultured podocytes and glomeruli of diabetic rats and patients using in vitro and in vivo approaches. Podocyte injury was assessed by migration, invasion and apoptosis assay. Biological parameters were analyzed using enzyme-linked immunosorbent assay. We found that high glucose stimulated miR-27a expression, which, by negatively targeting PPARγ, activated β-catenin signaling as evidenced by upregulation of β-catenin target genes, snail1 and α-smooth muscle actin (α-SMA) and downregulation of podocyte-specific markers podocin and synaptopodin. These changes caused podocyte injury as demonstrated by increased podocyte mesenchymal transition, disrupted podocyte architectural integrity and increased podocyte apoptosis. Furthermore, we provide evidence that miR-27a contributed to unfavorable renal function and increased podocyte injury in diabetic rats. Notably, miR-27a exhibited clinical and biological relevance as it was linked to elevated serum creatinine, proteinuria and reduced creatinine clearance rate. In addition, miR-27a upregulation and activation of PPARγ/β-catenin signaling were verified in renal biopsy samples from DN patients. We propose a novel role of the miR-27a/PPARγ/β-catenin axis in fostering the progression toward more deteriorated podocyte injury in DN. Targeting miR-27a could be a potential therapeutic approach for DN.

Introduction: To investigate the effect of Atorvastatin (ATO) and Rosuvastatin (ROS) on blood lipid, high sensitivity CRP (hs-CRP), interleukin-6 (IL-6), albumin (ALB), prealbumin (PA), and transferring (TF) in maintenance hemodialysis (MHD) patients. Methods: Eighty MHD patients were enrolled and divided into two groups: ROS and ATO. Patients in Group ROS (n = 38) received ROS (10 mg/day), and those in group ATO (n = 42) received ATO (20 mg/day) for 12 weeks, respectively. Findings: Administration of ROS and ATO both significantly reduced the concentrations of TC, LDL-C, TG, hs-CRP, and IL-6, but increased high-density lipoproteincholesterol (HDL-C), ALB, PA, and TF levels. Furthermore, the level of LDL-C decreased more significantly with inhibited microinflammation and improved nutrition situation in ROS group compared with ATO group. ATO and ROS not only decreased blood lipid levels but also inhibited the microinflammatory state and improved nutrition situation in MHD patients. Discussion: The results have shown that ROS is better than ATO in the treatment of MHD patients.

Background: The prognosis of non-small-cell lung cancer (NSCLC) is poor yet mechanistic understanding and therapeutic options remain limited. We investigated the biological and clinical significance of microRNA-130b and its relationship with apoptosis in NSCLC. Methods: The level of microRNA-130b in relationship with the expression of PPARγ, VEGF-A, BCL-2 and apoptosis were analyzed in 91 lung cancer patient samples using immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on tissue microarrays. Gain and loss-of-function studies were performed to investigate the effects of microRNA-130b, peroxisome proliferator-activated receptor γ (PPARγ) or vascular endothelial growth factor-A (VEGF-A) on biological functions of lung cancer cells using in vitro and in vivo approaches. Results: MicroRNA-130b up-regulation conferred unfavorable prognosis of lung cancer patients. Notably, microRNA-130b targeted PPARγ and inhibiting microRNA-130b markedly repressed proliferation, invasion and metastasis of lung cancer cells, leading to increased apoptosis. MicroRNA-130b-dependent biologic effects were due to suppression of PPARγ that in turn activated BCL-2, the key mediator of anti-apoptosis. Administration of microRNA-130b mimic to mouse xenografts promoted tumor growth. In vitro and in vivo, miR-130b enrichment associated with down-regulation of PPARγ, up-regulation of VEGF-A and BCL-2, and decreased apoptosis. Conclusions: The present study demonstrates that microRNA-130b promotes lung cancer progression via PPARγ/VEGF-A/BCL-2-mediated suppression of apoptosis. Targeting microRNA-130b might have remarkable therapeutic potential for lung cancer therapy.

MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγ pathway in diabetic nephropathy