Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy
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 explo...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.748225/full |
| _version_ | 1818930892076220416 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Shuo-Ming Ou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T04:07:55Z |
| format | Article |
| id | doaj.art-56cb477fab1946c390ed0f1710c1d258 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-20T04:07:55Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-56cb477fab1946c390ed0f1710c1d2582022-12-21T19:53:59ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-11-01810.3389/fmed.2021.748225748225Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney BiopsyShuo-Ming Ou0Shuo-Ming Ou1Shuo-Ming Ou2Shuo-Ming Ou3Shuo-Ming Ou4Shuo-Ming Ou5Ming-Tsun Tsai6Ming-Tsun Tsai7Ming-Tsun Tsai8Ming-Tsun Tsai9Ming-Tsun Tsai10Ming-Tsun Tsai11Huan-Yuan Chen12Fu-An Li13Wei-Cheng Tseng14Wei-Cheng Tseng15Wei-Cheng Tseng16Wei-Cheng Tseng17Wei-Cheng Tseng18Wei-Cheng Tseng19Kuo-Hua Lee20Kuo-Hua Lee21Kuo-Hua Lee22Kuo-Hua Lee23Kuo-Hua Lee24Kuo-Hua Lee25Fu-Pang Chang26Fu-Pang Chang27Yao-Ping Lin28Yao-Ping Lin29Yao-Ping Lin30Yao-Ping Lin31Yao-Ping Lin32Yao-Ping Lin33Ruey-Bing Yang34Der-Cherng Tarng35Der-Cherng Tarng36Der-Cherng Tarng37Der-Cherng Tarng38Der-Cherng Tarng39Der-Cherng Tarng40Der-Cherng Tarng41Der-Cherng Tarng42Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, TaiwanDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, TaiwanDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, TaiwanDepartment of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, TaiwanInflammation and Immunity Research Center, National Yang-Ming University, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanDivision of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanSchool of Medicine, National Yang-Ming University, Taipei, TaiwanSchool of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCenter for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan0Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan1Department and Institute of Physiology, National Yang Ming Chiao Tung University, Taipei, TaiwanBackground: 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.748225/fullgalectin-3chronic kidney diseasetubular atrophyinterstitial fibrosiskidney biopsyRNA-sequencing analysis |
| spellingShingle | 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 Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy Frontiers in Medicine galectin-3 chronic kidney disease tubular atrophy interstitial fibrosis kidney biopsy RNA-sequencing analysis |
| title | Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy |
| title_full | Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy |
| title_fullStr | Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy |
| title_full_unstemmed | Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy |
| title_short | Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy |
| title_sort | identification of galectin 3 as potential biomarkers for renal fibrosis by rna sequencing and clinicopathologic findings of kidney biopsy |
| topic | galectin-3 chronic kidney disease tubular atrophy interstitial fibrosis kidney biopsy RNA-sequencing analysis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.748225/full |
| work_keys_str_mv | AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT shuomingou identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT mingtsuntsai identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT huanyuanchen identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT fuanli identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT weichengtseng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT kuohualee identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT fupangchang identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT fupangchang identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT yaopinglin identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT rueybingyang identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy AT dercherngtarng identificationofgalectin3aspotentialbiomarkersforrenalfibrosisbyrnasequencingandclinicopathologicfindingsofkidneybiopsy |