• Assessment of Fibrinogen-like...

Treffer: Assessment of Fibrinogen-like 2 (FGL2) in Human Chronic Kidney Disease through Transcriptomics Data Analysis.

Title:
Assessment of Fibrinogen-like 2 (FGL2) in Human Chronic Kidney Disease through Transcriptomics Data Analysis.
Authors:
Denicolò S; Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria., Nair V; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA., Leierer J; Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria., Rudnicki M; Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria., Kretzler M; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA., Mayer G; Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria., Ju W; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA., Perco P; Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria.
Source:
Biomolecules [Biomolecules] 2022 Dec 31; Vol. 13 (1). Date of Electronic Publication: 2022 Dec 31.
Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
English
Journal Info:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, 2011-
MeSH Terms:
Transcriptome* , Renal Insufficiency, Chronic*/genetics, Mice ; Animals ; Humans ; Endothelial Cells/metabolism ; Fibrinogen/metabolism ; Fibrosis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
References:
Exp Biol Med (Maywood). 2014 Feb;239(2):193-201. (PMID: 24414480)
Clin Kidney J. 2017 Apr;10(2):176-187. (PMID: 28584625)
Sci Adv. 2019 Nov 13;5(11):eaax0629. (PMID: 31763448)
Nephrol Dial Transplant. 2018 Feb 1;33(2):310-318. (PMID: 28339906)
J Biol Chem. 2001 Nov 30;276(48):45184-92. (PMID: 11579091)
Am J Pathol. 2010 Oct;177(4):1674-86. (PMID: 20847290)
PLoS One. 2015 Mar 12;10(3):e0119686. (PMID: 25763980)
Lancet. 2020 Feb 29;395(10225):709-733. (PMID: 32061315)
Sci Transl Med. 2015 Dec 02;7(316):316ra193. (PMID: 26631632)
J Immunol. 2012 Jul 15;189(2):988-1001. (PMID: 22723521)
Kidney Int. 2011 Nov;80(10):1035-44. (PMID: 21734641)
Science. 2015 Jan 23;347(6220):1260419. (PMID: 25613900)
Diabetes. 2011 Sep;60(9):2354-69. (PMID: 21752957)
Am J Pathol. 2010 Feb;176(2):594-607. (PMID: 20019191)
Diabetes. 2006 Nov;55(11):2993-3003. (PMID: 17065335)
J Biomed Res. 2011 Mar;25(2):120-7. (PMID: 23554679)
Nephron Exp Nephrol. 2005;101(2):e42-9. (PMID: 15942256)
J Transl Med. 2014 Feb 23;12:53. (PMID: 24559374)
World J Clin Infect Dis. 2013 Aug 25;3(3):37-46. (PMID: 26161303)
J Immunol. 2005 Jun 1;174(11):7403-11. (PMID: 15905589)
Nat Rev Nephrol. 2014 Apr;10(4):226-37. (PMID: 24514753)
Genome Res. 2013 Nov;23(11):1862-73. (PMID: 23950145)
JCI Insight. 2019 Jun 20;4(12):. (PMID: 31217356)
Kidney Int. 2013 Apr;83(4):749-56. (PMID: 23325076)
J Thromb Haemost. 2016 Jan;14(1):40-7. (PMID: 26564405)
Biomed Pharmacother. 2020 Oct;130:110468. (PMID: 32795921)
Adv Chronic Kidney Dis. 2017 Mar;24(2):117-129. (PMID: 28284377)
PLoS One. 2015 Aug 28;10(8):e0136994. (PMID: 26317775)
Int Rev Immunol. 2016 Jul 3;35(4):325-339. (PMID: 25259408)
Kidney Int. 2020 Dec;98(6):1502-1518. (PMID: 33038424)
Genomics. 2001 Feb 1;71(3):330-8. (PMID: 11170750)
Thromb Haemost. 2013 Aug;110(2):295-307. (PMID: 23739922)
Nat Rev Nephrol. 2019 Mar;15(3):144-158. (PMID: 30692665)
JCI Insight. 2021 Jun 8;6(11):. (PMID: 33974569)
J Immunol. 2008 Jan 1;180(1):249-60. (PMID: 18097026)
Nat Rev Nephrol. 2014 Sep;10(9):493-503. (PMID: 24981817)
Eur J Clin Invest. 2016 Mar;46(3):213-26. (PMID: 26707063)
PLoS One. 2010 Oct 18;5(10):e13451. (PMID: 20976140)
Biochem Biophys Res Commun. 2001 Feb 2;280(4):1036-41. (PMID: 11162631)
Grant Information:
UH3 DK114923 United States DK NIDDK NIH HHS; U01 DK133090 United States DK NIDDK NIH HHS; U54 DK083912 United States DK NIDDK NIH HHS; UH3 DK114920 United States DK NIDDK NIH HHS; UH3 DK114870 United States DK NIDDK NIH HHS; U2C DK114886 United States DK NIDDK NIH HHS; UH3 DK114908 United States DK NIDDK NIH HHS; UH3 DK114915 United States DK NIDDK NIH HHS; UH3 DK114926 United States DK NIDDK NIH HHS; P30 DK081943 United States DK NIDDK NIH HHS; U2CTR002818 United States NS NINDS NIH HHS; UH3 DK114933 United States DK NIDDK NIH HHS; UH3 DK114937 United States DK NIDDK NIH HHS; U45DK083912 United States DK NIDDK NIH HHS; UH3 DK114907 United States DK NIDDK NIH HHS; UH3 DK114866 United States DK NIDDK NIH HHS; P30 DK020572 United States DK NIDDK NIH HHS; UH3 DK114861 United States DK NIDDK NIH HHS
Contributed Indexing:
Keywords: FGL2; chronic kidney disease; gene expression; outcome analysis; renal fibrosis
Substance Nomenclature:
9001-32-5 (Fibrinogen)
0 (RNA, Messenger)
0 (FGL2 protein, human)
Entry Date(s):
Date Created: 20230121 Date Completed: 20230124 Latest Revision: 20231110
Update Code:
20250114
PubMed Central ID:
PMC9855364
DOI:
10.3390/biom13010089
PMID:
36671474
Database:
MEDLINE

Weitere Informationen

Fibrinogen-like 2 (FGL2) was recently found to be associated with fibrosis in a mouse model of kidney damage and was proposed as a potential therapeutic target in chronic kidney disease (CKD). We assessed the association of renal FGL2 mRNA expression with the disease outcome in two independent CKD cohorts (NEPTUNE and Innsbruck CKD cohort) using Kaplan Meier survival analysis. The regulation of FGL2 in kidney biopsies of CKD patients as compared to healthy controls was further assessed in 13 human CKD transcriptomics datasets. The FGL2 protein expression in human renal tissue sections was determined via immunohistochemistry. The regulators of FGL2 mRNA expression in renal tissue were identified in the co-expression and upstream regulator analysis of FGL2-positive renal cells via the use of single-cell RNA sequencing data from the kidney precision medicine project (KPMP). Higher renal FGL2 mRNA expression was positively associated with kidney fibrosis and negatively associated with eGFR. Renal FGL2 mRNA expression was upregulated in CKD as compared with healthy controls and associated with CKD progression in the Innsbruck CKD cohort ( p -value = 0.0036) and NEPTUNE cohort ( p -value = 0.0048). The highest abundance of FGL2 protein in renal tissue was detected in the thick ascending limb of the loop of Henle and macula densa, proximal tubular cells, as well as in glomerular endothelial cells. The upstream regulator analysis identified TNF, IL1B, IFNG, NFKB1, and SP1 as factors potentially inducing FGL2-co-expressed genes, whereas factors counterbalancing FGL2-co-expressed genes included GLI1, HNF1B, or PPARGC1A. In conclusion, renal FGL2 mRNA expression is elevated in human CKD, and higher FGL2 levels are associated with fibrosis and worse outcomes.