Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose

Suk Hee Lee; Jong Sup Bae; Sun Hee Park; Byung Heon Lee; Rang Woon Park; Je Yong Choi; Jae Yong Park; Sung Woo Ha; Yong Lim Kim; Tae Hwan Kwon; In San Kim

doi:10.1046/j.1523-1755.2003.00158.x

Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose

Suk Hee Lee, Jong Sup Bae, Sun Hee Park, Byung Heon Lee, Rang Woon Park, Je Yong Choi, Jae Yong Park, Sung Woo Ha, Yong Lim Kim, Tae Hwan Kwon, In San Kim

Kyungpook National University

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased by transforming growth factor-β (TGF-β). TGF-β is believed to be involved in the development of diabetic nephropathy and thus we have assessed the possibility that βig-h3 may be a down-stream molecule in this pathogenic process. Methods. Immunoblotting and immunohistochemistry were done using an antibody against mouse βig-h3 protein. βig-h3 and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion and migration were assessed by measuring activity of N-acetyl-β-D-glucosaminidase and using a transwell plate, respectively. Results. Immunohistochemistry revealed that βig-h3 occurs mainly in the basement membrane of proximal tubules, particularly the S3 segment but also to lesser extents in the basement membranes of the cortical thick ascending limb cells and the parietal glomerular epithelial cells in Bowman's capsule. Immunoblotting revealed that ∼68 kD bands were seen only in the cortex + the outer stripe of the outer medulla. Rats with streptozotocin (STZ)-induced diabetes exhibited a marked and sustained increase in renal βig-h3 abundance. This was mirrored by urinary βig-h3 levels. In vitro experiments with human primary renal proximal tubular epithelial cells revealed that their expression of βig-h3 was greatly increased by either TGF-β or glucose. High glucose levels also stimulated TGF-β production by renal proximal tubular epithelial cells and the high glucose-induced βig-h3 expression was almost completely blocked by anti-TGF-β antibody. βig-h3 mediated renal proximal tubular epithelial cells adhesion and migration. Conclusion. βig-h3 may be important in the development of diabetic nephropathy. Furthermore, the level of urinary βig-h3 may be useful as an early marker reflecting disease onset and progression.

Original language	English
Pages (from-to)	1012-1021
Number of pages	10
Journal	Kidney International
Volume	64
Issue number	3
DOIs	https://doi.org/10.1046/j.1523-1755.2003.00158.x
State	Published - 1 Sep 2003

Keywords

Diabetes mellitus
Integrin
Proximal tubule
Renal failure
Tubulointerstitial fibrosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1046/j.1523-1755.2003.00158.x

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Lee, S. H., Bae, J. S., Park, S. H., Lee, B. H., Park, R. W., Choi, J. Y., Park, J. Y., Ha, S. W., Kim, Y. L., Kwon, T. H., & Kim, I. S. (2003). Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose. Kidney International, 64(3), 1012-1021. https://doi.org/10.1046/j.1523-1755.2003.00158.x

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title = "Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose",

abstract = "Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased by transforming growth factor-β (TGF-β). TGF-β is believed to be involved in the development of diabetic nephropathy and thus we have assessed the possibility that βig-h3 may be a down-stream molecule in this pathogenic process. Methods. Immunoblotting and immunohistochemistry were done using an antibody against mouse βig-h3 protein. βig-h3 and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion and migration were assessed by measuring activity of N-acetyl-β-D-glucosaminidase and using a transwell plate, respectively. Results. Immunohistochemistry revealed that βig-h3 occurs mainly in the basement membrane of proximal tubules, particularly the S3 segment but also to lesser extents in the basement membranes of the cortical thick ascending limb cells and the parietal glomerular epithelial cells in Bowman's capsule. Immunoblotting revealed that ∼68 kD bands were seen only in the cortex + the outer stripe of the outer medulla. Rats with streptozotocin (STZ)-induced diabetes exhibited a marked and sustained increase in renal βig-h3 abundance. This was mirrored by urinary βig-h3 levels. In vitro experiments with human primary renal proximal tubular epithelial cells revealed that their expression of βig-h3 was greatly increased by either TGF-β or glucose. High glucose levels also stimulated TGF-β production by renal proximal tubular epithelial cells and the high glucose-induced βig-h3 expression was almost completely blocked by anti-TGF-β antibody. βig-h3 mediated renal proximal tubular epithelial cells adhesion and migration. Conclusion. βig-h3 may be important in the development of diabetic nephropathy. Furthermore, the level of urinary βig-h3 may be useful as an early marker reflecting disease onset and progression.",

keywords = "Diabetes mellitus, Integrin, Proximal tubule, Renal failure, Tubulointerstitial fibrosis",

author = "Lee, {Suk Hee} and Bae, {Jong Sup} and Park, {Sun Hee} and Lee, {Byung Heon} and Park, {Rang Woon} and Choi, {Je Yong} and Park, {Jae Yong} and Ha, {Sung Woo} and Kim, {Yong Lim} and Kwon, {Tae Hwan} and Kim, {In San}",

year = "2003",

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doi = "10.1046/j.1523-1755.2003.00158.x",

language = "English",

volume = "64",

pages = "1012--1021",

journal = "Kidney International",

issn = "0085-2538",

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Lee, SH, Bae, JS, Park, SH, Lee, BH , Park, RW , Choi, JY, Park, JY, Ha, SW, Kim, YL, Kwon, TH & Kim, IS 2003, 'Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose', Kidney International, vol. 64, no. 3, pp. 1012-1021. https://doi.org/10.1046/j.1523-1755.2003.00158.x

TY - JOUR

T1 - Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose

AU - Lee, Suk Hee

AU - Bae, Jong Sup

AU - Park, Sun Hee

AU - Lee, Byung Heon

AU - Park, Rang Woon

AU - Choi, Je Yong

AU - Park, Jae Yong

AU - Ha, Sung Woo

AU - Kim, Yong Lim

AU - Kwon, Tae Hwan

AU - Kim, In San

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased by transforming growth factor-β (TGF-β). TGF-β is believed to be involved in the development of diabetic nephropathy and thus we have assessed the possibility that βig-h3 may be a down-stream molecule in this pathogenic process. Methods. Immunoblotting and immunohistochemistry were done using an antibody against mouse βig-h3 protein. βig-h3 and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion and migration were assessed by measuring activity of N-acetyl-β-D-glucosaminidase and using a transwell plate, respectively. Results. Immunohistochemistry revealed that βig-h3 occurs mainly in the basement membrane of proximal tubules, particularly the S3 segment but also to lesser extents in the basement membranes of the cortical thick ascending limb cells and the parietal glomerular epithelial cells in Bowman's capsule. Immunoblotting revealed that ∼68 kD bands were seen only in the cortex + the outer stripe of the outer medulla. Rats with streptozotocin (STZ)-induced diabetes exhibited a marked and sustained increase in renal βig-h3 abundance. This was mirrored by urinary βig-h3 levels. In vitro experiments with human primary renal proximal tubular epithelial cells revealed that their expression of βig-h3 was greatly increased by either TGF-β or glucose. High glucose levels also stimulated TGF-β production by renal proximal tubular epithelial cells and the high glucose-induced βig-h3 expression was almost completely blocked by anti-TGF-β antibody. βig-h3 mediated renal proximal tubular epithelial cells adhesion and migration. Conclusion. βig-h3 may be important in the development of diabetic nephropathy. Furthermore, the level of urinary βig-h3 may be useful as an early marker reflecting disease onset and progression.

AB - Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased by transforming growth factor-β (TGF-β). TGF-β is believed to be involved in the development of diabetic nephropathy and thus we have assessed the possibility that βig-h3 may be a down-stream molecule in this pathogenic process. Methods. Immunoblotting and immunohistochemistry were done using an antibody against mouse βig-h3 protein. βig-h3 and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion and migration were assessed by measuring activity of N-acetyl-β-D-glucosaminidase and using a transwell plate, respectively. Results. Immunohistochemistry revealed that βig-h3 occurs mainly in the basement membrane of proximal tubules, particularly the S3 segment but also to lesser extents in the basement membranes of the cortical thick ascending limb cells and the parietal glomerular epithelial cells in Bowman's capsule. Immunoblotting revealed that ∼68 kD bands were seen only in the cortex + the outer stripe of the outer medulla. Rats with streptozotocin (STZ)-induced diabetes exhibited a marked and sustained increase in renal βig-h3 abundance. This was mirrored by urinary βig-h3 levels. In vitro experiments with human primary renal proximal tubular epithelial cells revealed that their expression of βig-h3 was greatly increased by either TGF-β or glucose. High glucose levels also stimulated TGF-β production by renal proximal tubular epithelial cells and the high glucose-induced βig-h3 expression was almost completely blocked by anti-TGF-β antibody. βig-h3 mediated renal proximal tubular epithelial cells adhesion and migration. Conclusion. βig-h3 may be important in the development of diabetic nephropathy. Furthermore, the level of urinary βig-h3 may be useful as an early marker reflecting disease onset and progression.

KW - Diabetes mellitus

KW - Integrin

KW - Proximal tubule

KW - Renal failure

KW - Tubulointerstitial fibrosis

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U2 - 10.1046/j.1523-1755.2003.00158.x

DO - 10.1046/j.1523-1755.2003.00158.x

M3 - Article

C2 - 12911551

AN - SCOPUS:12444325813

SN - 0085-2538

VL - 64

SP - 1012

EP - 1021

JO - Kidney International

JF - Kidney International

IS - 3

ER -

Expression of TGF-β-induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose

Abstract

Keywords

UN SDGs

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