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

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

doi:10.3389/fmed.2021.748225

Abstract

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.

Highlights

Chronic kidney disease (CKD) remains a major public health problem and is one of the leading causes of mortality and morbidity worldwide [1,2,3]
Urinary samples were collected from the patients, and the urine albumin-to-creatinine ratio (UACR) and urine protein-to-creatinine ratio (UPCR) were calculated
Of the 249 study participants, we divided the study participants into three groups based on the tertile of plasma Gal-3 levels (1039.9 pg/mL, respectively)

Summary

Introduction

Chronic kidney disease (CKD) remains a major public health problem and is one of the leading causes of mortality and morbidity worldwide [1,2,3]. CKD patients are generally asymptomatic, so it is difficult to recognize the early clinical signs or symptoms of CKD [4]. Current biomarkers, such as serum blood urea nitrogen, serum creatinine and proteinuria, lack sensitivity for the early detection of the development of CKD [5, 6]. If we can identify these patients in the early disease stage, their renal function decline may be slowed or even reversed. 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

Objectives

Methods

Results

Conclusion