Galectin-1 is a new fibrosis protein in type 1 and type 2 diabetes

Noor Al-Obaidi, Sumathy Mohan, Sitai Liang, Zhenze Zhao, Bijaya K. Nayak, Boajie Li, P. Sriramarao, Samy L. Habib

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Chronic exposure of tubular renal cells to high glucose contributes to tubulointerstitial changes in diabetic nephropathy. In the present study, we identified a new fibrosis gene called galectin-1 (Gal-1), which is highly expressed in tubular cells of kidneys of type 1 and type 2 diabeticmouse models. Gal-1 protein and mRNA expression showed significant increase in kidney cortex of heterozygous Akita+/2 and db/db mice compared with wild-type mice.Mouse proximal tubular cells exposed to high glucose showed significant increase in phosphorylationofAkt andGal-1.We clonedGal-1 promoter and identified the transcription factorAP4asbindingtotheGal-1 promoter to up-regulate its function. Transfection of cells with plasmid carrying mutations in the binding sites of AP4 to Gal-1 promoter resulted in decreased protein function of Gal-1. In addition, inhibition ofGal-1 by OTX-008 showed significant decrease in p-Akt/AP4 and protein-promoter activity of Gal-1 and fibronectin. Moreover, downregulation of AP4 by small interfering RNA resulted in a significant decrease in protein expression and promoter activity ofGal-1.We found that kidney of Gal-12/2 mice express very lowlevels of fibronectin protein. In summary, Gal-1 is highly expressed in kidneys of type 1 and 2 diabetic mice, and AP4 is a major transcription factor that activates Gal-1 under hyperglycemia. Inhibition of Gal-1 by OTX-008 blocks activation of Akt and prevents accumulation ofGal-1, suggesting a novel role ofGal-1 inhibitor as a possible therapeutic target to treat renal fibrosis in diabetes.

Original languageEnglish (US)
Pages (from-to)373-387
Number of pages15
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Gal-1
  • IDDM
  • NIDDM
  • Renal fibrosis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Galectin-1 is a new fibrosis protein in type 1 and type 2 diabetes'. Together they form a unique fingerprint.

Cite this