Upregulated Long Noncoding RNA LOC105375913 Induces Tubulointerstitial Fibrosis in Focal Segmental Glomerulosclerosis

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jan 26

PMID 30679767

Citations 21

Authors

Runhong Han

Shuai Hu

Weisong Qin

Jingsong Shi

Caihong Zeng

Hao Bao

Zhihong Liu

Affiliations

Soon will be listed here.

Abstract

Tubulointerstitial fibrosis impacts renal prognosis of focal segmental glomerulosclerosis (FSGS). Based on transcriptomic analysis, we found that the level of LOC105375913 was increased in tubular cells of FSGS patients. C3a induced the expression of LOC105375913, which promoted the expression of fibronectin and collagen I in tubular cells. Silence of snail reversed the level of fibronectin and collagen I in cells overexpressing LOC105375913. MiR-27b was predicted and confirmed to regulate the expression of snail in tubular cells, and LOC105375913 contained the response element of miR-27b. The competitive binding between LOC105375913 and miR-27b increased the level of snail and promoted fibrogenesis in tubular cells. Upstream, p38 and XBP-1s regulated the expression of LOC105375913. Inhibition of p38 or silence of XBP-1s decreased the level of LOC105375913, and suppressed the expression of snail, fibronectin and collagen I in tubular cells treated with C3a. Overexpression of LOC105375913 decreased the level of miR-27b, increased the level of snail and caused tubulointerstitial fibrosis in mice. In conclusion, the activation of C3a/p38/XBP-1s pathway induces the expression of LOC105375913 in tubular cells, and LOC105375913 increases the level of snail and induces tubulointerstitial fibrosis through competitive binding of miR-27b in tubular cells of FSGS patients.

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References

Alexopoulos E, Stangou M, Papagianni A, Pantzaki A, Papadimitriou M . Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2000; 15(9):1348-56. DOI: 10.1093/ndt/15.9.1348. View

Kalluri R, Neilson E . Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003; 112(12):1776-84. PMC: 297008. DOI: 10.1172/JCI20530. View

Stambe C, Atkins R, Tesch G, Masaki T, Schreiner G, Nikolic-Paterson D . The role of p38alpha mitogen-activated protein kinase activation in renal fibrosis. J Am Soc Nephrol. 2004; 15(2):370-9. DOI: 10.1097/01.asn.0000109669.23650.56. View

Yoshino J, Monkawa T, Tsuji M, Inukai M, Itoh H, Hayashi M . Snail1 is involved in the renal epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2007; 362(1):63-68. DOI: 10.1016/j.bbrc.2007.07.146. View

Sebe A, Leivonen S, Fintha A, Masszi A, Rosivall L, Kahari V . Transforming growth factor-beta-induced alpha-smooth muscle cell actin expression in renal proximal tubular cells is regulated by p38beta mitogen-activated protein kinase, extracellular signal-regulated protein kinase1,2 and the Smad signalling.... Nephrol Dial Transplant. 2008; 23(5):1537-45. DOI: 10.1093/ndt/gfm789. View

Tang Z, Lu B, Hatch E, Sacks S, Sheerin N . C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy. J Am Soc Nephrol. 2009; 20(3):593-603. PMC: 2653680. DOI: 10.1681/ASN.2008040434. View

Nonne N, Ameyar-Zazoua M, Souidi M, Harel-Bellan A . Tandem affinity purification of miRNA target mRNAs (TAP-Tar). Nucleic Acids Res. 2009; 38(4):e20. PMC: 2831319. DOI: 10.1093/nar/gkp1100. View

Gupta R, Shah N, Wang K, Kim J, Horlings H, Wong D . Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010; 464(7291):1071-6. PMC: 3049919. DOI: 10.1038/nature08975. View

Yang L, Besschetnova T, Brooks C, Shah J, Bonventre J . Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 2010; 16(5):535-43, 1p following 143. PMC: 3928013. DOI: 10.1038/nm.2144. View

10.

Zaferani A, Vives R, van der Pol P, Hakvoort J, Navis G, Goor H . Identification of tubular heparan sulfate as a docking platform for the alternative complement component properdin in proteinuric renal disease. J Biol Chem. 2010; 286(7):5359-67. PMC: 3037648. DOI: 10.1074/jbc.M110.167825. View

11.

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi P . A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?. Cell. 2011; 146(3):353-8. PMC: 3235919. DOI: 10.1016/j.cell.2011.07.014. View

12.

DAgati V, Kaskel F, Falk R . Focal segmental glomerulosclerosis. N Engl J Med. 2011; 365(25):2398-411. DOI: 10.1056/NEJMra1106556. View

13.

Bao H, Ge Y, Zhuang S, Dworkin L, Liu Z, Gong R . Inhibition of glycogen synthase kinase-3β prevents NSAID-induced acute kidney injury. Kidney Int. 2012; 81(7):662-73. PMC: 3305839. DOI: 10.1038/ki.2011.443. View

14.

Zhao S, Zhu L, Duan H, Liu S, Liu Q, Liu W . PI3K/Akt pathway mediates high glucose-induced lipid accumulation in human renal proximal tubular cells via spliced XBP-1. J Cell Biochem. 2012; 113(10):3288-98. DOI: 10.1002/jcb.24207. View

15.

Tang X, Xu F, Chen D, Zeng C, Liu Z . The clinical course and long-term outcome of primary focal segmental glomerulosclerosis in Chinese adults. Clin Nephrol. 2013; 80(2):130-9. DOI: 10.5414/CN107607. View

16.

Trempolec N, Dave-Coll N, Nebreda A . SnapShot: p38 MAPK substrates. Cell. 2013; 152(4):924-924.e1. DOI: 10.1016/j.cell.2013.01.047. View

17.

Lv X, Lian G, Wang H, Song E, Yao H, Wang M . Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One. 2013; 8(5):e63516. PMC: 3662674. DOI: 10.1371/journal.pone.0063516. View

18.

Zhou M, Ma H, Lin H, Qin J . Induction of epithelial-to-mesenchymal transition in proximal tubular epithelial cells on microfluidic devices. Biomaterials. 2013; 35(5):1390-401. DOI: 10.1016/j.biomaterials.2013.10.070. View

19.

Bao H, Chen H, Zhu X, Zhang M, Yao G, Yu Y . MiR-223 downregulation promotes glomerular endothelial cell activation by upregulating importin α4 and α5 in IgA nephropathy. Kidney Int. 2013; 85(3):624-35. DOI: 10.1038/ki.2013.469. View

20.

Bao H, Hu S, Zhang C, Shi S, Qin W, Zeng C . Inhibition of miRNA-21 prevents fibrogenic activation in podocytes and tubular cells in IgA nephropathy. Biochem Biophys Res Commun. 2014; 444(4):455-60. DOI: 10.1016/j.bbrc.2014.01.065. View