Tags

Type your tag names separated by a space and hit enter

Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis.
Am J Physiol Renal Physiol. 2005 Apr; 288(4):F800-9.AJ

Abstract

Matrix accumulation in the renal tubulointerstitium is predictive of a progressive decline in renal function. Transforming growth factor-beta(1) (TGF-beta(1)) and, more recently, connective tissue growth factor (CTGF) are recognized to play key roles in mediating the fibrogenic response, independently of the primary renal insult. Further definition of the independent and interrelated effects of CTGF and TGF-beta(1) is critical for the development of effective antifibrotic strategies. CTGF (20 ng/ml) induced fibronectin and collagen IV secretion in primary cultures of human proximal tubule cells (PTC) and cortical fibroblasts (CF) compared with control values (P < 0.005 in all cases). This effect was inhibited by neutralizing antibodies to either TGF-beta or to the TGF-beta type II receptor (TbetaRII). TGF-beta(1) induced a greater increase in fibronectin and collagen IV secretion in both PTC (P < 0.01) and CF (P < 0.01) compared with that observed with CTGF alone. The combination of TGF-beta(1) and CTGF was additive in their effects on both PTC and CF fibronectin and collagen IV secretion. TGF-beta(1) (2 ng/ml) stimulated CTGF mRNA expression within 30 min, which was sustained for up to 24 h, with a consequent increase in CTGF protein (P < 0.05), whereas CTGF had no effect on TGF-beta(1) mRNA or protein expression. TGF-beta(1) (2 ng/ml) induced phosphorylated (p)Smad-2 within 15 min, which was sustained for up to 24 h. CTGF had a delayed effect on increasing pSmad-2 expression, which was evident at 24 h. In conclusion, this study has demonstrated the key dependence of the fibrogenic actions of CTGF on TGF-beta. It has further uniquely demonstrated that CTGF requires TGF-beta, signaling through the TbetaRII in both PTCs and CFs, to exert its fibrogenic response in this in vitro model.

Authors+Show Affiliations

Dept. of Medicine, Level 3, Wallace Freeborn Professorial Block, Royal North Shore Hospital, St. Leonards, New South Wales, Australia 2065, USA.No affiliation info availableNo affiliation info availableNo 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

15536170

Citation

Qi, W, et al. "Integrated Actions of Transforming Growth Factor-beta1 and Connective Tissue Growth Factor in Renal Fibrosis." American Journal of Physiology. Renal Physiology, vol. 288, no. 4, 2005, pp. F800-9.
Qi W, Twigg S, Chen X, et al. Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis. Am J Physiol Renal Physiol. 2005;288(4):F800-9.
Qi, W., Twigg, S., Chen, X., Polhill, T. S., Poronnik, P., Gilbert, R. E., & Pollock, C. A. (2005). Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis. American Journal of Physiology. Renal Physiology, 288(4), F800-9.
Qi W, et al. Integrated Actions of Transforming Growth Factor-beta1 and Connective Tissue Growth Factor in Renal Fibrosis. Am J Physiol Renal Physiol. 2005;288(4):F800-9. PubMed PMID: 15536170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis. AU - Qi,W, AU - Twigg,S, AU - Chen,X, AU - Polhill,T S, AU - Poronnik,P, AU - Gilbert,R E, AU - Pollock,C A, Y1 - 2004/11/09/ PY - 2004/11/13/pubmed PY - 2005/4/19/medline PY - 2004/11/13/entrez SP - F800 EP - 9 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 288 IS - 4 N2 - Matrix accumulation in the renal tubulointerstitium is predictive of a progressive decline in renal function. Transforming growth factor-beta(1) (TGF-beta(1)) and, more recently, connective tissue growth factor (CTGF) are recognized to play key roles in mediating the fibrogenic response, independently of the primary renal insult. Further definition of the independent and interrelated effects of CTGF and TGF-beta(1) is critical for the development of effective antifibrotic strategies. CTGF (20 ng/ml) induced fibronectin and collagen IV secretion in primary cultures of human proximal tubule cells (PTC) and cortical fibroblasts (CF) compared with control values (P < 0.005 in all cases). This effect was inhibited by neutralizing antibodies to either TGF-beta or to the TGF-beta type II receptor (TbetaRII). TGF-beta(1) induced a greater increase in fibronectin and collagen IV secretion in both PTC (P < 0.01) and CF (P < 0.01) compared with that observed with CTGF alone. The combination of TGF-beta(1) and CTGF was additive in their effects on both PTC and CF fibronectin and collagen IV secretion. TGF-beta(1) (2 ng/ml) stimulated CTGF mRNA expression within 30 min, which was sustained for up to 24 h, with a consequent increase in CTGF protein (P < 0.05), whereas CTGF had no effect on TGF-beta(1) mRNA or protein expression. TGF-beta(1) (2 ng/ml) induced phosphorylated (p)Smad-2 within 15 min, which was sustained for up to 24 h. CTGF had a delayed effect on increasing pSmad-2 expression, which was evident at 24 h. In conclusion, this study has demonstrated the key dependence of the fibrogenic actions of CTGF on TGF-beta. It has further uniquely demonstrated that CTGF requires TGF-beta, signaling through the TbetaRII in both PTCs and CFs, to exert its fibrogenic response in this in vitro model. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/15536170/Integrated_actions_of_transforming_growth_factor_beta1_and_connective_tissue_growth_factor_in_renal_fibrosis_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00179.2004?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -