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Secretion of collagen type IV by human renal fibroblasts is increased by high glucose via a TGF-beta-independent pathway.
Nephrol Dial Transplant. 2004 Jul; 19(7):1694-701.ND

Abstract

BACKGROUND

Tubulointerstitial fibrosis is an important component of diabetic nephropathy, which is characterized by increased expression of interstitial extracellular matrix components and aberrant expression of the basement membrane component collagen type IV. The present study examined the effect of high ambient glucose and transforming growth factor-beta1 (TGF-beta1) on collagen secretion by human renal fibroblasts and proximal tubular epithelial cells (PTECs).

METHODS

Human renal fibroblasts (TK173) and PTECs (HK2) were used to examine the effects of high glucose (25 mM d-glucose) and TGF-beta1 (1 ng/ml) on collagen type I, III and IV secretion compared with control medium (5.5 mM glucose). Matrix components were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

Renal fibroblasts are the main producers of the interstitial components collagen type I and type III, while collagen type IV was secreted predominantly by PTECs. However, renal fibroblasts were also able to secrete collagen type IV. Secretion of collagen type IV by fibroblasts was increased upon stimulation with TGF-beta1, reaching levels comparable with those secreted by TGF-beta1-induced PTECs. Moreover, high glucose stimulated increased collagen type IV secretion. Importantly, this could not be attenuated by neutralizing pan-specific anti-TGF-beta antibodies.

CONCLUSIONS

These data show that renal fibroblasts secrete collagen type IV, which can be increased by high glucose independent of endogenous TGF-beta. This suggests that as well as the increased expression of interstitial components, renal fibroblasts can contribute to the increased expression of the basement membrane component collagen type IV in tubulointerstitial fibrosis observed during diabetic nephropathy.

Authors+Show Affiliations

Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15150349

Citation

Lam, Suzanne, et al. "Secretion of Collagen Type IV By Human Renal Fibroblasts Is Increased By High Glucose Via a TGF-beta-independent Pathway." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 19, no. 7, 2004, pp. 1694-701.
Lam S, van der Geest RN, Verhagen NA, et al. Secretion of collagen type IV by human renal fibroblasts is increased by high glucose via a TGF-beta-independent pathway. Nephrol Dial Transplant. 2004;19(7):1694-701.
Lam, S., van der Geest, R. N., Verhagen, N. A., Daha, M. R., & van Kooten, C. (2004). Secretion of collagen type IV by human renal fibroblasts is increased by high glucose via a TGF-beta-independent pathway. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 19(7), 1694-701.
Lam S, et al. Secretion of Collagen Type IV By Human Renal Fibroblasts Is Increased By High Glucose Via a TGF-beta-independent Pathway. Nephrol Dial Transplant. 2004;19(7):1694-701. PubMed PMID: 15150349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Secretion of collagen type IV by human renal fibroblasts is increased by high glucose via a TGF-beta-independent pathway. AU - Lam,Suzanne, AU - van der Geest,Reinier N, AU - Verhagen,Nicole A M, AU - Daha,Mohamed R, AU - van Kooten,Cees, Y1 - 2004/05/18/ PY - 2004/5/20/pubmed PY - 2004/12/16/medline PY - 2004/5/20/entrez SP - 1694 EP - 701 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 19 IS - 7 N2 - BACKGROUND: Tubulointerstitial fibrosis is an important component of diabetic nephropathy, which is characterized by increased expression of interstitial extracellular matrix components and aberrant expression of the basement membrane component collagen type IV. The present study examined the effect of high ambient glucose and transforming growth factor-beta1 (TGF-beta1) on collagen secretion by human renal fibroblasts and proximal tubular epithelial cells (PTECs). METHODS: Human renal fibroblasts (TK173) and PTECs (HK2) were used to examine the effects of high glucose (25 mM d-glucose) and TGF-beta1 (1 ng/ml) on collagen type I, III and IV secretion compared with control medium (5.5 mM glucose). Matrix components were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Renal fibroblasts are the main producers of the interstitial components collagen type I and type III, while collagen type IV was secreted predominantly by PTECs. However, renal fibroblasts were also able to secrete collagen type IV. Secretion of collagen type IV by fibroblasts was increased upon stimulation with TGF-beta1, reaching levels comparable with those secreted by TGF-beta1-induced PTECs. Moreover, high glucose stimulated increased collagen type IV secretion. Importantly, this could not be attenuated by neutralizing pan-specific anti-TGF-beta antibodies. CONCLUSIONS: These data show that renal fibroblasts secrete collagen type IV, which can be increased by high glucose independent of endogenous TGF-beta. This suggests that as well as the increased expression of interstitial components, renal fibroblasts can contribute to the increased expression of the basement membrane component collagen type IV in tubulointerstitial fibrosis observed during diabetic nephropathy. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/15150349/Secretion_of_collagen_type_IV_by_human_renal_fibroblasts_is_increased_by_high_glucose_via_a_TGF_beta_independent_pathway_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfh235 DB - PRIME DP - Unbound Medicine ER -