Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy

Ji Li Jin, Ha Lee Sun, Ki Kim Dong, Ri Jin, Dong Sub Jung, Seung Jae Kwak, Hye Kim Seung, SeungHyeok Han, Eun Lee Jung, Jin Moon Sung, Dong Ryeol Ryu, TaeHyun Yoo, Suk Han Dae, Shin-Wook Kang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10-8 M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RTPCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immuno-histochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P = 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P = 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume297
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1

Fingerprint

Colchicine
Diabetic Nephropathies
Extracellular Matrix
Chemokine CCL2
Intercellular Adhesion Molecule-1
Fibronectins
Kidney
Messenger RNA
Staining and Labeling
Glucose
Albuminuria
Mesangial Cells
Streptozocin
Culture Media
Real-Time Polymerase Chain Reaction
Albumins
Cultured Cells
Proteins
Anti-Inflammatory Agents
Western Blotting

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Jin, Ji Li ; Sun, Ha Lee ; Dong, Ki Kim ; Jin, Ri ; Jung, Dong Sub ; Kwak, Seung Jae ; Seung, Hye Kim ; Han, SeungHyeok ; Jung, Eun Lee ; Sung, Jin Moon ; Ryu, Dong Ryeol ; Yoo, TaeHyun ; Dae, Suk Han ; Kang, Shin-Wook. / Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy. In: American Journal of Physiology - Renal Physiology. 2009 ; Vol. 297, No. 1.
@article{3287a56ff1a94b4caa27c0865d58b0da,
title = "Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy",
abstract = "Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10-8 M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RTPCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immuno-histochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P = 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P = 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.",
author = "Jin, {Ji Li} and Sun, {Ha Lee} and Dong, {Ki Kim} and Ri Jin and Jung, {Dong Sub} and Kwak, {Seung Jae} and Seung, {Hye Kim} and SeungHyeok Han and Jung, {Eun Lee} and Sung, {Jin Moon} and Ryu, {Dong Ryeol} and TaeHyun Yoo and Dae, {Suk Han} and Shin-Wook Kang",
year = "2009",
month = "7",
day = "1",
doi = "10.1152/ajprenal.90649.2008",
language = "English",
volume = "297",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1",

}

Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy. / Jin, Ji Li; Sun, Ha Lee; Dong, Ki Kim; Jin, Ri; Jung, Dong Sub; Kwak, Seung Jae; Seung, Hye Kim; Han, SeungHyeok; Jung, Eun Lee; Sung, Jin Moon; Ryu, Dong Ryeol; Yoo, TaeHyun; Dae, Suk Han; Kang, Shin-Wook.

In: American Journal of Physiology - Renal Physiology, Vol. 297, No. 1, 01.07.2009.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy

AU - Jin, Ji Li

AU - Sun, Ha Lee

AU - Dong, Ki Kim

AU - Jin, Ri

AU - Jung, Dong Sub

AU - Kwak, Seung Jae

AU - Seung, Hye Kim

AU - Han, SeungHyeok

AU - Jung, Eun Lee

AU - Sung, Jin Moon

AU - Ryu, Dong Ryeol

AU - Yoo, TaeHyun

AU - Dae, Suk Han

AU - Kang, Shin-Wook

PY - 2009/7/1

Y1 - 2009/7/1

N2 - Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10-8 M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RTPCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immuno-histochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P = 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P = 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

AB - Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10-8 M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RTPCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immuno-histochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P = 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P = 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

UR - http://www.scopus.com/inward/record.url?scp=67650661945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650661945&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.90649.2008

DO - 10.1152/ajprenal.90649.2008

M3 - Article

VL - 297

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1931-857X

IS - 1

ER -