Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy f...

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Main Authors: Kyeong-Seok Kim, Jin-Sol Lee, Jae-Hyeon Park, Eun-Young Lee, Jong-Seok Moon, Sangkyu Lee, Jong-Sil Lee, Jung-Hwan Kim, Hyung-Sik Kim
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Biomedicines
Subjects:
CFD
C4b
Online Access:https://www.mdpi.com/2227-9059/9/5/457
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spelling doaj-688cee5892f849d7b0d12f2ed0fbe5382021-04-22T23:05:05ZengMDPI AGBiomedicines2227-90592021-04-01945745710.3390/biomedicines9050457Identification of Novel Biomarker for Early Detection of Diabetic NephropathyKyeong-Seok Kim0Jin-Sol Lee1Jae-Hyeon Park2Eun-Young Lee3Jong-Seok Moon4Sangkyu Lee5Jong-Sil Lee6Jung-Hwan Kim7Hyung-Sik Kim8School of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaDepartment of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, KoreaDepartment of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan 31151, KoreaBK21 Plus KNU Multi‐Omics Based Creative Drug Research Team, College of Pharmacy, Kyungpook National University, Daegu 41566, KoreaDepartment of Pathology, Institute of Health Sciences, College of Medicine, Gyeongsang National University Hospital, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaDiabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.https://www.mdpi.com/2227-9059/9/5/457RNA-sequencingbiomarkerurineCFDCXCR6C4b
collection DOAJ
language English
format Article
sources DOAJ
author Kyeong-Seok Kim
Jin-Sol Lee
Jae-Hyeon Park
Eun-Young Lee
Jong-Seok Moon
Sangkyu Lee
Jong-Sil Lee
Jung-Hwan Kim
Hyung-Sik Kim
spellingShingle Kyeong-Seok Kim
Jin-Sol Lee
Jae-Hyeon Park
Eun-Young Lee
Jong-Seok Moon
Sangkyu Lee
Jong-Sil Lee
Jung-Hwan Kim
Hyung-Sik Kim
Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
Biomedicines
RNA-sequencing
biomarker
urine
CFD
CXCR6
C4b
author_facet Kyeong-Seok Kim
Jin-Sol Lee
Jae-Hyeon Park
Eun-Young Lee
Jong-Seok Moon
Sangkyu Lee
Jong-Sil Lee
Jung-Hwan Kim
Hyung-Sik Kim
author_sort Kyeong-Seok Kim
title Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
title_short Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
title_full Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
title_fullStr Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
title_full_unstemmed Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy
title_sort identification of novel biomarker for early detection of diabetic nephropathy
publisher MDPI AG
series Biomedicines
issn 2227-9059
publishDate 2021-04-01
description Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.
topic RNA-sequencing
biomarker
urine
CFD
CXCR6
C4b
url https://www.mdpi.com/2227-9059/9/5/457
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