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Original Research
Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b
Si F Sun, Patrick MK Tang, Min Feng, Xiao Jun, Xiao R Huang, Ping Li, Ronal CW Ma and Hui Y Lan
Diabetes 2017 Dec; db170816. https://doi.org/10.2337/db17-0816
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Abstract

TGF-β/Smad signaling plays an important role in diabetic nephropathy. The present study identified a novel Smad3-dependent long non-coding RNA (lncRNA) Erbb4-IR in the development of type-2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and was specifically induced by AGE via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN such as elevated microalbuminuria, serum creatinine and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs). Mechanistically, we identified that the Erbb4-IR-miR-29b axis was a key mechanism of T2DN because Erbb4-IR was able to bind the 3’UTR of miR-29b genomic sequence to suppress miR-29b expression at transcriptional level. In contrast, silencing of renal Erbb4-IR increased miR-29b and therefore protected kidney from progressive renal injury in db/db mice and prevented mTECs and mMCs from AGE-induced loss of miR-29b and fibrotic response in vitro. Collectively, we identify that Erbb4-IR is a Smad3-dependent lncRNA that promotes renal fibrosis in T2DN by suppressing miR-29b. Targeting Erbb4-IR may represent a novel therapy for T2DN.

Footnotes

  • * S.F. Sun and P.M.K. Tang are equally contributed in this work

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db17-0816.

  • Received July 11, 2017.
  • Accepted November 29, 2017.
  • © 2017 by the American Diabetes Association.
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Diabetes: 67 (5)

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May 2018
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Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b
Si F Sun, Patrick MK Tang, Min Feng, Xiao Jun, Xiao R Huang, Ping Li, Ronal CW Ma, Hui Y Lan
Diabetes Dec 2017, db170816; DOI: 10.2337/db17-0816

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Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b
Si F Sun, Patrick MK Tang, Min Feng, Xiao Jun, Xiao R Huang, Ping Li, Ronal CW Ma, Hui Y Lan
Diabetes Dec 2017, db170816; DOI: 10.2337/db17-0816
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