Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model
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Ameliorated renal function has been reported after bariatric surgery, but the mechanisms underlying this phenomenon are not well-studied. To investigate whether the long non-coding RNA (lncRNA) MALAT1 mediates the amelioration of diabetic nephropathy after duodenal-jejunal bypass (DJB) surgery, rats were assigned randomly into four groups: diabetic (DM) group, DM with DJB surgery group, DM with sham surgery group, and healthy control group. Food intake, body weight, oral glucose tolerance test (OGTT), urine albumin excretion rate (UAER), and glomerular filtration rate (GFR) were measured and histological examination of renal sections was performed. For in vitro study, HK-2 cells were cultured under various glucose concentrations following MALAT1 siRNA transfection. Expression levels of MALAT1, SAA3, IL-6, and TNF-α in rat renal tissues or HK-2 cell lines were evaluated by qRT-PCR and/or ELISA. Results showed DJB surgery improved the renal function of diabetic rats, as indicated by ameliorated UAER and GFR and attenuated glomerular hypertrophy. Expression of MALAT1 and its downstream target SAA3 was significantly downregulated in renal tissues after DJB, which in turn decreased the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions. Our findings suggest that MALAT1 is implicated in the improvement of renal function after DJB through regulation of its downstream targets SAA3, IL-6, and TNF-α.
KeywordsDiabetes mellitus Duodenal-jejunal bypass Long non-coding RNA MALAT1 Renal function
This study was supported by grants from the National Natural Science Foundation of China (grant No. 81600059, 81471019/H0712), the Natural Science Foundation of Shandong Province (grant No. ZR2014HQ004), and the Fundamental Research Funds of Shandong University (grant No. 2014QLKY22).
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Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, ... & Agyemang C (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390:2627–2642Google Scholar
- 13.Geloneze B, Geloneze SR, Chaim E, Hirsch FF, Felici AC, Lambert G, Tambascia MA, Pareja JC (2012) Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study. Ann Surg 256:72–78CrossRefPubMedGoogle Scholar
- 15.Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zornig M, MacLeod AR, Spector DL, Diederichs S (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189CrossRefPubMedGoogle Scholar
- 17.Kitada K, Nakano D, Ohsaki H, Hitomi H, Minamino T, Yatabe J, Felder RA, Mori H, Masaki T, Kobori H, Nishiyama A (2014) Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J Diabetes Complicat 28:604–611CrossRefPubMedPubMedCentralGoogle Scholar
- 25.NCD Risk Factor Collaboration (2016) Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387:1513–1530Google Scholar
- 30.Sjostrom L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden A, Bouchard C, Carlsson B, Karason K, Lonroth H, Naslund I, Sjostrom E, Taube M, Wedel H, Svensson PA, Sjoholm K, Carlsson LM (2014) Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA 311:2297–2304CrossRefPubMedGoogle Scholar
- 32.Song P, Yang S, Xiao L, Xu X, Tang C, Yang Y, Ma M, Zhu J, Liu F, Sun L (2014, 2014) PKCdelta promotes high glucose induced renal tubular oxidative damage via regulating activation and translocation of p66Shc. Oxidative Med Cell Longev:746531Google Scholar