Altered Expression of Long Noncoding and Messenger RNAs in Diabetic Nephropathy following Treatment with Rosiglitazone

Abstract

Diabetic nephropathy (DN) is characterized by metabolic disorder and inflammation. However, the regulatory effects that long noncoding RNAs (lncRNAs) have on the pathogenesis of DN and on the efficacy of rosiglitazone treatment have yet to be clearly defined. Herein, we performed unbiased RNA sequencing to characterize the transcriptomic profiles in db/db diabetic mouse model with or without rosiglitazone treatment that served to improve the phenotypes of DN. Moreover, RNA-seq profiling revealed that the development of DN caused an upregulation in the expression of 1176 mRNAs and a downregulation in the expression of 1010 mRNAs compared to controls, with the expression of 251 mRNAs being returned to normal following treatment with rosiglitazone. Further, 88 upregulated and 68 downregulated lncRNAs were identified in db/db mice compared to controls, 10 of which had their normal expression restored following treatment with rosiglitazone. Bioinformatic analysis revealed that the primary pathways involved in the pathogenesis of DN, and subsequently in the therapeutic effects of PPARc, are related to inflammatory and metabolic processes. From bioinformatics analysis, lncRNA-AI838599 emerged as a novel molecular mechanism for rosiglitazone treatment in DN through TNFα-NFκb pathway. ese findings may indicate a new molecular regulatory approach for the development of DN therapeutic agents.

Integrative ATAC‐seq and RNA‐seq analysis associated with diabetic nephropathy and identification of novel targets for treatment by dapagliflozin

“…40 Studies suggested that KLF10, KLF11, KLF13, KLF4, and KLF5 may be related to DN and KLF15 loss exacerbated acute kidney injury and fibrosis. 16,41 The public human database showed that KLF6 was significantly downregulated in the DN versus healthy living donor, which was in line with our study showing that KLF6 had decreasing trend in CG versus Controls. Furthermore, we observed that DAPA treatment had the tendency to reverse this downward trend, which possibly underlined the new renoprotective mechanism of DAPA.…”

Rosiglitazone attenuates high glucose-induced proliferation, inflammation, oxidative stress and extracellular matrix accumulation in mouse mesangial cells through the Gm26917/miR-185-5p pathway

“…Though several lncRNAs are functionally explored in DN models, there are still a large number of lncRNAs whose functions are unknown. Gm26917 was reported to upregulated in renal cortical tissues from DN mouse models, while its expression was reduced after RSG treatment [15]. In function, Gm2619 was shown to promote the Gm26917 knockdown suppressed HG-induced proliferation, oxidative stress, inflammation and ECM accumulation, while Gm26917 overexpression partly abolished the effects of RSG and recovered these injuries, suggesting that Gm26917 might contribute to the development of DN.…”

“…RSG treatment could affect the expression of long non-coding RNAs (lncRNAs) in mouse models with DN [15], indicating that lncRNAs were involved in RSGregulated DN progression. LncRNAs are members of non-coding RNAs, with over 200 nucleotides in length.…”

“…It was documented that lncRNAs were implicated in DN development by regulating numerous pathologic processes in mesangial cells, such as ECM accumulating, oxidative stress or microRNA (miRNA) suppression [18,19]. Gm26917 was a predicted lncRNA that was highly expressed in renal cortical tissues from DN mice but downregulated after RSG treatment [15]. However, the function of Gm26917 is still lacking.…”

Danhong injection represses diabetic retinopathy and nephropathy advancement in diabetic mice by upregulating microRNA-30d-5p and targeting JAK1

“…Pathologically, DN is characterized by changes in renal function and structure which can lead to renal insufficiency, renal fibrosis, podocyte damage, and end-stage renal disease [ 7 ]. Current treatments for DN contain rosiglitazone [ 8 ], tripterygium glycosides [ 9 ] and so on. Although there is a certain therapeutic effect in the treatments, it is also accompanied by some adverse reactions, including abnormal liver function, leukopenia, irregular menstruation, etc.…”