Frontiers in Medicine (Nov 2021)

Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy

  • Shuo-Ming Ou,
  • Shuo-Ming Ou,
  • Shuo-Ming Ou,
  • Shuo-Ming Ou,
  • Shuo-Ming Ou,
  • Shuo-Ming Ou,
  • Ming-Tsun Tsai,
  • Ming-Tsun Tsai,
  • Ming-Tsun Tsai,
  • Ming-Tsun Tsai,
  • Ming-Tsun Tsai,
  • Ming-Tsun Tsai,
  • Huan-Yuan Chen,
  • Fu-An Li,
  • Wei-Cheng Tseng,
  • Wei-Cheng Tseng,
  • Wei-Cheng Tseng,
  • Wei-Cheng Tseng,
  • Wei-Cheng Tseng,
  • Wei-Cheng Tseng,
  • Kuo-Hua Lee,
  • Kuo-Hua Lee,
  • Kuo-Hua Lee,
  • Kuo-Hua Lee,
  • Kuo-Hua Lee,
  • Kuo-Hua Lee,
  • Fu-Pang Chang,
  • Fu-Pang Chang,
  • Yao-Ping Lin,
  • Yao-Ping Lin,
  • Yao-Ping Lin,
  • Yao-Ping Lin,
  • Yao-Ping Lin,
  • Yao-Ping Lin,
  • Ruey-Bing Yang,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng,
  • Der-Cherng Tarng

DOI
https://doi.org/10.3389/fmed.2021.748225
Journal volume & issue
Vol. 8

Abstract

Read online

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.

Keywords