Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis

Tzu Hao Huang, Hao Ai Shui, Shuk Man Ka, Bor Luen Tang, Tai Kuang Chao, Jin Shuen Chen, Yuh Feng Lin, Ann Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. Rab23, a member of the Rab family of small GTPase, has a function in antagonizing sonic hedgehog signal transduction. Both Rab-family and hedgehog-related proteins are involved in sclerosis and fibrosis in certain pathological states, but their roles in focal segmental glomerulosclerosis (FSGS) remain unclear. Methods. The FSGS model was established in Balb/c mice by a single injection of adriamycin. Serum, urine and mice kidneys were collected on Days 0, 7, 15 and 20. Western blot analysis was performed to detect the levels of Rab23 in the samples. Immunohistochemistry was used to examine the expressional profiles of Rab23 in kidneys. The expressions of transcripts of Rab23, extracellular matrix (ECM) proteins, and various hedgehog signalling pathway genes in kidneys or mesangial cells were evaluated by real-time RT-PCR. The effect of Rab23 on ECM protein expressions was evaluated by the knockdown or overexpression of Rab23 in mesangial cells. Results. Our results show that elevations of Rab23 were observed in the urine, but not in the serum, of the FSGS mice. Rab23 and hedgehog signalling pathway genes were constitutively expressed in normal kidneys and were significantly up-regulated in the kidneys of FSGS mice. The basal expression of Rab23 was identified in glomeruli, and mesangial cells displayed obvious elevation of Rab23 in the FSGS state. The knockdown or overexpression of Rab23 affected the collagen expression in cultured mesangial cells. Conclusions. An autocrine loop of hedgehog signalling could be activated in mesangial cells in the FSGS state, and Rab23 may be elevated to suppress hedgehog signalling and/or influence collagen synthesis. Importantly, Rab23 could serve as a biomarker that indicates the severity of FSGS.

Original languageEnglish
Pages (from-to)743-754
Number of pages12
JournalNephrology Dialysis Transplantation
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

Fingerprint

Focal Segmental Glomerulosclerosis
Mesangial Cells
Hedgehogs
Kidney
Extracellular Matrix Proteins
Collagen
Hedgehog Proteins
Urine
Monomeric GTP-Binding Proteins
Sclerosis
Serum
Doxorubicin
Genes
Real-Time Polymerase Chain Reaction
Cultured Cells
Signal Transduction
Fibrosis
Biomarkers
Western Blotting
Immunohistochemistry

Keywords

  • Biomarker
  • Focal segmental glomerulosclerosis
  • Hedgehog signal transduction
  • Mesangial cells
  • Rab23

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis. / Huang, Tzu Hao; Shui, Hao Ai; Ka, Shuk Man; Tang, Bor Luen; Chao, Tai Kuang; Chen, Jin Shuen; Lin, Yuh Feng; Chen, Ann.

In: Nephrology Dialysis Transplantation, Vol. 24, No. 3, 03.2009, p. 743-754.

Research output: Contribution to journalArticle

Huang, Tzu Hao ; Shui, Hao Ai ; Ka, Shuk Man ; Tang, Bor Luen ; Chao, Tai Kuang ; Chen, Jin Shuen ; Lin, Yuh Feng ; Chen, Ann. / Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis. In: Nephrology Dialysis Transplantation. 2009 ; Vol. 24, No. 3. pp. 743-754.
@article{4376aeb79fd04e7c92f6a984c0f1b758,
title = "Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis",
abstract = "Background. Rab23, a member of the Rab family of small GTPase, has a function in antagonizing sonic hedgehog signal transduction. Both Rab-family and hedgehog-related proteins are involved in sclerosis and fibrosis in certain pathological states, but their roles in focal segmental glomerulosclerosis (FSGS) remain unclear. Methods. The FSGS model was established in Balb/c mice by a single injection of adriamycin. Serum, urine and mice kidneys were collected on Days 0, 7, 15 and 20. Western blot analysis was performed to detect the levels of Rab23 in the samples. Immunohistochemistry was used to examine the expressional profiles of Rab23 in kidneys. The expressions of transcripts of Rab23, extracellular matrix (ECM) proteins, and various hedgehog signalling pathway genes in kidneys or mesangial cells were evaluated by real-time RT-PCR. The effect of Rab23 on ECM protein expressions was evaluated by the knockdown or overexpression of Rab23 in mesangial cells. Results. Our results show that elevations of Rab23 were observed in the urine, but not in the serum, of the FSGS mice. Rab23 and hedgehog signalling pathway genes were constitutively expressed in normal kidneys and were significantly up-regulated in the kidneys of FSGS mice. The basal expression of Rab23 was identified in glomeruli, and mesangial cells displayed obvious elevation of Rab23 in the FSGS state. The knockdown or overexpression of Rab23 affected the collagen expression in cultured mesangial cells. Conclusions. An autocrine loop of hedgehog signalling could be activated in mesangial cells in the FSGS state, and Rab23 may be elevated to suppress hedgehog signalling and/or influence collagen synthesis. Importantly, Rab23 could serve as a biomarker that indicates the severity of FSGS.",
keywords = "Biomarker, Focal segmental glomerulosclerosis, Hedgehog signal transduction, Mesangial cells, Rab23",
author = "Huang, {Tzu Hao} and Shui, {Hao Ai} and Ka, {Shuk Man} and Tang, {Bor Luen} and Chao, {Tai Kuang} and Chen, {Jin Shuen} and Lin, {Yuh Feng} and Ann Chen",
year = "2009",
month = "3",
doi = "10.1093/ndt/gfn570",
language = "English",
volume = "24",
pages = "743--754",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis

AU - Huang, Tzu Hao

AU - Shui, Hao Ai

AU - Ka, Shuk Man

AU - Tang, Bor Luen

AU - Chao, Tai Kuang

AU - Chen, Jin Shuen

AU - Lin, Yuh Feng

AU - Chen, Ann

PY - 2009/3

Y1 - 2009/3

N2 - Background. Rab23, a member of the Rab family of small GTPase, has a function in antagonizing sonic hedgehog signal transduction. Both Rab-family and hedgehog-related proteins are involved in sclerosis and fibrosis in certain pathological states, but their roles in focal segmental glomerulosclerosis (FSGS) remain unclear. Methods. The FSGS model was established in Balb/c mice by a single injection of adriamycin. Serum, urine and mice kidneys were collected on Days 0, 7, 15 and 20. Western blot analysis was performed to detect the levels of Rab23 in the samples. Immunohistochemistry was used to examine the expressional profiles of Rab23 in kidneys. The expressions of transcripts of Rab23, extracellular matrix (ECM) proteins, and various hedgehog signalling pathway genes in kidneys or mesangial cells were evaluated by real-time RT-PCR. The effect of Rab23 on ECM protein expressions was evaluated by the knockdown or overexpression of Rab23 in mesangial cells. Results. Our results show that elevations of Rab23 were observed in the urine, but not in the serum, of the FSGS mice. Rab23 and hedgehog signalling pathway genes were constitutively expressed in normal kidneys and were significantly up-regulated in the kidneys of FSGS mice. The basal expression of Rab23 was identified in glomeruli, and mesangial cells displayed obvious elevation of Rab23 in the FSGS state. The knockdown or overexpression of Rab23 affected the collagen expression in cultured mesangial cells. Conclusions. An autocrine loop of hedgehog signalling could be activated in mesangial cells in the FSGS state, and Rab23 may be elevated to suppress hedgehog signalling and/or influence collagen synthesis. Importantly, Rab23 could serve as a biomarker that indicates the severity of FSGS.

AB - Background. Rab23, a member of the Rab family of small GTPase, has a function in antagonizing sonic hedgehog signal transduction. Both Rab-family and hedgehog-related proteins are involved in sclerosis and fibrosis in certain pathological states, but their roles in focal segmental glomerulosclerosis (FSGS) remain unclear. Methods. The FSGS model was established in Balb/c mice by a single injection of adriamycin. Serum, urine and mice kidneys were collected on Days 0, 7, 15 and 20. Western blot analysis was performed to detect the levels of Rab23 in the samples. Immunohistochemistry was used to examine the expressional profiles of Rab23 in kidneys. The expressions of transcripts of Rab23, extracellular matrix (ECM) proteins, and various hedgehog signalling pathway genes in kidneys or mesangial cells were evaluated by real-time RT-PCR. The effect of Rab23 on ECM protein expressions was evaluated by the knockdown or overexpression of Rab23 in mesangial cells. Results. Our results show that elevations of Rab23 were observed in the urine, but not in the serum, of the FSGS mice. Rab23 and hedgehog signalling pathway genes were constitutively expressed in normal kidneys and were significantly up-regulated in the kidneys of FSGS mice. The basal expression of Rab23 was identified in glomeruli, and mesangial cells displayed obvious elevation of Rab23 in the FSGS state. The knockdown or overexpression of Rab23 affected the collagen expression in cultured mesangial cells. Conclusions. An autocrine loop of hedgehog signalling could be activated in mesangial cells in the FSGS state, and Rab23 may be elevated to suppress hedgehog signalling and/or influence collagen synthesis. Importantly, Rab23 could serve as a biomarker that indicates the severity of FSGS.

KW - Biomarker

KW - Focal segmental glomerulosclerosis

KW - Hedgehog signal transduction

KW - Mesangial cells

KW - Rab23

UR - http://www.scopus.com/inward/record.url?scp=60749131946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60749131946&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfn570

DO - 10.1093/ndt/gfn570

M3 - Article

VL - 24

SP - 743

EP - 754

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 3

ER -