SNHG16/miR-205/HDAC5 is involved in the progression of renal fibrosis.

Renal interstitial fibrosis (RIF) represents an irreversible and progressive pathological manifestation of chronic renal disease, which ultimately leads to end-stage renal disease. Long noncoding RNAs (lncRNAs) have been suggested to be involved in the progression of RIF. Small nucleolar RNA host gene 16 (SNHG16), a member of lncRNAs, has been found to be involved in the progression of pulmonary fibrosis. This paper first researched the effect of SNHG16 on renal fibrosis. We established a unilateral ureteral obstruction (UUO)-induced mouse RIF model by ligation of the left ureter to evaluate the biological function of SNHG16 in RIF. As a result, SNHG16 was upregulated in UUO-induced renal fibrotic tissues. Knockdown of SNHG16 inhibited RIF and reduced alpha-smooth muscle actin (α-SMA), fibronectin, and college IV expression. miR-205 was a target of SNHG16, and downregulated in UUO-induced renal fibrotic tissues. Inhibition of miR-205 promoted RIF and increased the expression of α-SMA, college IV, and fibronectin. Overexpression of SNHG16 promoted the UUO-induced RIF, but miR-205 abrogated this effect of SNHG16. Histone deacetylase 5 (HDAC5) showed high expression in UUO-induced renal fibrotic tissues. Knockdown of HDAC5 significantly reduced α-SMA, fibronectin, and college IV expression in renal tissues of UUO-induced mice. Inhibition of miR-205 promoted HDAC5 expression, but knockdown of SNHG16 inhibited HDAC5 expression in renal tissues of UUO-induced mice. In conclusion, SHNG16 is highly expressed in renal fibrotic tissues of UUO-induced mice. Knockdown of SHNG16 may prevent UUO-induced RIF by indirectly upregulating HDAC5 via targeting miR-205. SHNG16 may be novel target for treating renal fibrosis.

Role of reactive oxygen species in high concentration glucose-induced growth inhibition of human peritoneal mesothelial cells.

Background: To investigate the effects and mechanism of high concentration glucose (HG), exogenous hydrogen peroxide (H2O2), and antioxidants on the cell growth (cell proliferation) of human peritoneal mesothelial cells (HPMCs). Methods: All tests were conducted on cultured HPMCs (HMrSV5) in vitro. Various concentrations of glucose (0.1%, 1.35%, and 3.86%), H2O2 (0.5 and 0.1 mmol/L), and antioxidants (pyruvate and catalase) were used in cell culture. Moreover, in order to study the interaction between these factors, HG and H2O2, HG and antioxidants, HG, H2O2, and antioxidants, were used respectively. After 12-24 h, phase-contrast microscopy was used to examine the morphological changes of HPMCs. DNA synthesis was detected by 3H-thymidine incorporation to measure cell proliferation, and flow cytometry was used to evaluate the proportion of cells in G1 phase. Furthermore, semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) was utilized to determine the mRNA expression of p21Waf1 and p27Kip1 [cyclin-dependent kinase inhibitors (CKIs)], while immunocytochemistry (ICC) and Western blotting were employed to measure the protein expression of p21Waf1 and p27Kip1. Results: HG or low-dose exogenous H2O2 resulted in hypertrophy and senescence of HPMCs, resulting in similar morphological changes. Both HG and exogenous H2O2 (0.5 mmol/L) inhibited the proliferation of HPMCs and led to G1 phase arrest of HPMCs. The proportion of cells in G1 phase increased. Moreover, HG enhanced the toxic effects of exogenous H2O2. Both HG and exogenous H2O2 increased the expression of p21Waf1 and p27Kip1 . The addition of an antioxidant in HG medium arrested cells in the G1 phase and improved the inhibited cell proliferation. Conclusions: Both HG and exogenous H2O2 treatments can induce growth inhibition of HPMCs by arresting cell cycle progression, which is partially due to the increased expression of p21Waf1 and p27Kip1 . Thus, the effects of HG might be associated with endogenous reactive oxygen species (ROS), and it might be beneficial to use antioxidants in peritoneal dialysis (PD).

Risk factors for heart valve calcification in chronic kidney disease.

Cardiovascular disease (CVD) is a common cause of death in patients with chronic kidney disease (CKD). Aortic and mitral valve calcification (AVC and MVC, respectively) are critical indicators of CVD and all-cause mortality in CKD patients.We conducted a single center retrospective study of Chinese inpatients with CKD to identify risk factors associated with valve calcification (VC).Of 288 enrolled CKD patients, 22.9% had VC, all of which exhibited AVC, while 21.2% exhibited MVC. The VC group were significantly older than the non-VC group (70.42 ±â€Š11.83 vs 56.47 ±â€Š15.00, P < .001), and contained more patients with history of coronary artery disease (12.1% vs 4.5%, P = .025) or stroke (18.2% vs 5.4%, P < .001). Subjective global assessment scoring indicated that more VC patients were mid/severely malnourished. Levels of prealbumin, cholesterol (Ch), triglycerides, low-density lipoprotein (LDL), apolipoprotein E, ejection fraction, and fraction shortening were significantly lower, and blood C reactive protein, IL-6, left ventricular internal end diastole diameter measured in end diastole, and interventricular septum thickness (IVST) levels were significantly higher in the VC group. Bone metabolism did not differ significantly between the 2 groups. Multivariable logistic regression analysis indicated that age, blood Ch, and LDL levels were significantly associated with VC.Advanced age, increased IVST, hypocholesterolemia, and hyper-LDL cholesterolemia were key risk factors for VC in Han patients with CKD.

Effect of a low-protein diet supplemented with ketoacids on skeletal muscle atrophy and autophagy in rats with type 2 diabetic nephropathy.

A low-protein diet supplemented with ketoacids maintains nutritional status in patients with diabetic nephropathy. The activation of autophagy has been shown in the skeletal muscle of diabetic and uremic rats. This study aimed to determine whether a low-protein diet supplemented with ketoacids improves muscle atrophy and decreases the increased autophagy observed in rats with type 2 diabetic nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly divided into groups that received either a normal protein diet (NPD group), a low-protein diet (LPD group) or a low-protein diet supplemented with ketoacids (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as control animals and received a normal protein diet (control group). We found that protein restriction attenuated proteinuria and decreased blood urea nitrogen and serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group showed a delay in body weight loss, an attenuation in soleus muscle mass loss and a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62 and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the expression of autophagy-related genes; however, these differences were not statistically significant. In addition, LPD+KA abolished the upregulation of autophagy-related gene expression. Furthermore, the activation of autophagy in the NPD and LPD groups was confirmed by the appearance of autophagosomes or autolysosomes using electron microscopy, when compared with the Control and LPD+KA groups. Our results showed that LPD+KA abolished the activation of autophagy in skeletal muscle and decreased muscle loss in rats with type 2 diabetic nephropathy.

[Autophagy-lysosome pathway in skeletal muscle of diabetic nephropathy rats and the effect of low-protein diet plus α-keto acids on it].

OBJECTIVE: To explore the regulation of autophagy-lysosome pathway (ALP) in skeletal muscle of diabetic nephropathy and examine the effect of low protein diet plus α-keto acid on ALP. METHODS: A total of 45 24-week-old Goto-Kakizaki rats were randomized to receive normal protein (22%) diet (NPD), low-protein (6%) diet (LPD) or low-protein (5%) plus α-keto acids (1%) diet (Keto) (n = 15 each). Wistar control rats had a normal protein diet. The mRNA and protein levels of ALP markers LC3B, Bnip3, Cathepsin L in soleus muscle were evaluated at 48 weeks. Electron microscopy was used to confirm the changes of autophagy. RESULTS: Compared with CTL group, the mRNA levels of LC3B, Bnip3, Cathepsin L in soleus muscle of rats on NPD were higher, and protein levels of LC3B-I, LC3B-II, Bnip3, Cathepsin L in soleus muscle of rats on NPD also higher than CTL group (0.82 ± 0.33 vs 0.25 ± 0.07, 0.76 ± 0.38 vs 0.20 ± 0.12, 1.25 ± 0.30 vs 0.56 ± 0.19, 1.29 ± 0.40 vs 0.69 ± 0.20). The mRNA levels of LC3B, Bnip3 and Cathepsin L in LPD group were slightly lower, compared with NPD group. However there was no statistical significance. Similarly the protein levels of LC3B-I, LC3B-II, Bnip3 and Cathepsin L in LPD group were slightly lower with no statistical significance. In contrast, the mRNA levels of LC3B, Bnip3 and Cathepsin L were greatly lower in Keto group in comparison with NPD and LPD. And protein levels of LC3B-I, LC3B-II, Bnip3 and Cathepsin L were also greatly lower in Keto group in comparison with NPD and LPD. Additionally, autophagosome or auto-lysosome was found in NPD and LPD groups by electron microscopy. CONCLUSIONS: ALP is activated in skeletal muscle of diabetic nephropathy rats. And low protein plus α-keto acid decrease the activation of ALP and improve muscle wasting.