We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
LRNA9884, a Novel Smad3-Dependent Long Noncoding RNA, Promotes Diabetic Kidney Injury in / Mice via Enhancing MCP-1-Dependent Renal Inflammation.
- Authors
Ying-ying Zhang; Patrick Ming-Kuen Tang; Philip Chiu-Tsun Tang; Jun Xiao; Xiao-Ru Huang; Chen Yu; Ma, Ronald C. W.; Hui-Yao Lan; Zhang, Ying-Ying; Tang, Patrick Ming-Kuen; Tang, Philip Chiu-Tsun; Xiao, Jun; Huang, Xiao-Ru; Yu, Chen; Lan, Hui-Yao
- Abstract
Transforming growth factor-β/Smad3 signaling plays an important role in diabetic nephropathy, but its underlying working mechanism remains largely unexplored. The current study uncovered the pathogenic role and underlying mechanism of a novel Smad3-dependent long noncoding RNA (lncRNA) (LRNA9884) in type 2 diabetic nephropathy (T2DN). We found that LRNA9884 was significantly upregulated in the diabetic kidney of db/db mice at the age of 8 weeks preceding the onset of microalbuminuria and was associated with the progression of diabetic renal injury. LRNA9884 was induced by advanced glycation end products and tightly regulated by Smad3, and its levels were significantly blunted in db/db mice and cells lacking Smad3. More importantly, kidney-specific silencing of LRNA9884 effectively attenuated diabetic kidney injury in db/db mice, as shown by the reduction of histological injury, albuminuria excretion, and serum creatinine. Mechanistically, we identified that LRNA9884 promoted renal inflammation-driven T2DN by triggering MCP-1 production at the transcriptional level, and its direct binding significantly enhanced the promoter activity of MCP-1. Thus, LRNA9884 is a novel Smad3-dependent lncRNA that is highly expressed in db/db mice associated with T2DN development. Targeting of LRNA9884 effectively blocked MCP-1-dependent renal inflammation, therefore suppressing the progressive diabetic renal injury in db/db mice. This study reveals that LRNA9884 may be a novel and precision therapeutic target for T2DN in the future.
- Subjects
NON-coding RNA; KIDNEY injuries; ADVANCED glycation end-products; CREATININE; MICE; DIABETIC nephropathies
- Publication
Diabetes, 2019, Vol 68, Issue 7, p1485
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db18-1075