Ubiquitin-Fold Modifier-1 Participates in the Diabetic Inflammatory Response by Regulating NF-κB p65 Nuclear Translocation and the Ubiquitination and Degradation of IκBα

Drug Design, Development and Therapy
Xiaolei HuFengling Chen

Abstract

Ubiquitin-fold modifier-1 (Ufm1) is a recently identified ubiquitin-like protein. We previously confirmed that Ufm1 expression was increased in diabetic mice. However, its role in the development of diabetes remains undefined. Lentivirus-mediated gene knockdown and overexpression techniques were used to observe the effect of Ufm1 on the expression of inflammatory factors, adhesion molecules and chemokines, as well as the transcriptional activity of nuclear factor kappa-B (NF-κB) in macrophages. Western blot and immunofluorescence analyses were used to analyse the mechanism by which Ufm1 affects the transcriptional activity of NF-κB. Finally, the effects of Ufm1 on inflammation and pancreatic, renal and myocardial damage were observed in db/db mice. Knockdown of Ufm1 by lentivirus shRNA targeting Ufm1 (Lv-shUfm1) led to decreased secretion of IL-6, IL-1β, ICAM-1, VCAM-1, MCP-1 and CXCL2 in RAW264.7 cells that were exposed to LPS and TNF-α, while lentiviral overexpression of Ufm1 (Lv-Ufm1) caused the opposite effect. Interestingly, further investigation indicated that Ufm1 induced NF-κB p65 nuclear translocation in RAW264.7 cells via increasing the ubiquitination and degradation of IκBα. In an in vivo experiment, pretreatment of ...Continue Reading

References

May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·H HirotaT Taga
Oct 4, 1996·Cell·P A Baeuerle, D Baltimore
Sep 12, 1998·Molecular Cell·J M DesterroR T Hay
Jul 19, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Joseph J BoyleMartin R Bennett
Apr 29, 2005·Journal of the American Society of Nephrology : JASN·Fiona Y ChowGregory H Tesch
Aug 27, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Takayoshi SuganamiYoshihiro Ogawa
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasunari TakadaBharat B Aggarwal
Mar 28, 2009·Nature·Mark Hochstrasser
Dec 5, 2009·Journal of the American Society of Nephrology : JASN·Pengfei GongMichael J Ross
May 12, 2010·Cold Spring Harbor Perspectives in Biology·Toby Lawrence
Oct 31, 2012·International Journal of Molecular Sciences·Umar-Faruq CajeeMonde Ntwasa
Nov 28, 2012·Pharmacology & Therapeutics·Lyne FellmannPascal Bousquet
Apr 27, 2013·Nature·Thomas A WynnJeffrey W Pollard
Aug 6, 2013·Biochemical and Biophysical Research Communications·Wei HuangYong Xu
Aug 29, 2013·Journal of Diabetes Research·Md Shahidul Islam
Apr 10, 2014·International Journal of Molecular Medicine·Xiaolei HuFengling Chen
May 7, 2014·Diabetes Research and Clinical Practice·Nathalie EsserNicolas Paquot
Jul 19, 2014·Nephron. Experimental Nephrology·Boris Betz, Bryan R Conway
Oct 14, 2014·Frontiers in Immunology·Michael James KraakmanHélène L Kammoun
Apr 9, 2015·Frontiers in Endocrinology·Hee Min YooChin Ha Chung
Apr 29, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sudhanshu BhushanAndreas Meinhardt
May 23, 2015·Molecular Endocrinology·David L Morris
Jun 5, 2015·Journal of Atherosclerosis and Thrombosis·Qi PangFeng-Ling Chen
Jul 20, 2016·Pharmaceutical Research·Theodore J CoryCourtney V Fletcher
Sep 11, 2016·Immunobiology·Mohamed AhmedJan Van den Bossche
Apr 26, 2017·PeerJ·Xue HanGuo-Jun Jiang
Mar 20, 2018·Journal of Endocrinological Investigation·M I MaiorinoK Esposito

❮ Previous
Next ❯

Citations

Feb 14, 2021·Biomolecules·Katharina F Witting, Monique P C Mulder
Feb 2, 2021·Computational and Structural Biotechnology Journal·Hui LiuHanhui Ye
Oct 1, 2021·Nature Communications·Manoj KumarReuven Wiener

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
ELISA
confocal microscopy
Nuclear Translocation
ubiquitination
nuclear
sumoylation

Software Mentioned

SPSS
Gel
Image Pro Plus
ImageJ
Pro

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.