Renal fibrosis is not reduced by blocking transforming growth factor-β signaling in matrix-producing interstitial cells.

Abstract

Transforming growth factor-β (TGF-β) strongly promotes renal tubulointerstitial fibrosis, but the cellular target that mediates its profibrotic actions has not been clearly identified. While in vitro data suggest that TGF-β-induced matrix production is mediated by renal fibroblasts, the role of these cells in TGF-β-dependent tubulointerstitial fibrosis following renal injury is not well defined. To address this, we deleted the TGF-β type II receptor in matrix-producing interstitial cells using two different inducible Cre models: COL1A2-Cre with a mesenchymal enhancer element and tenascin-Cre that targets medullary interstitial cells, and either the mouse unilateral ureteral obstruction or the aristolochic acid renal injury model. Renal interstitial cells lacking the TGF-β receptor had significantly impaired collagen I production, but, unexpectedly, overall tissue fibrosis was unchanged in the conditional knockouts after renal injury. Thus, abrogating TGF-β signaling in matrix-producing interstitial cells is not sufficient to reduce fibrosis after renal injury.

• Authors: Surekha Neelisetty, Catherine Alford, Karen Reynolds, Luke Woodbury, Stellor Nlandu-Khodo, Haichun Yang, Agnes B Fogo, Chuan-Ming Hao, Raymond C Harris, Roy Zent, Leslie Gewin
• Journal: Kidney international (Kidney Int) Vol. 88 Issue 3 Pg. 503-14 (Sep 2015) ISSN: 1523-1755 [Electronic] United States
• PMID: 25760325 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• Aristolochic Acids
• Collagen Type I
• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• alpha-smooth muscle actin, mouse
• aristolochic acid I
• Receptor, Platelet-Derived Growth Factor beta
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Actins (metabolism)
• Animals
• Aristolochic Acids
• Cells, Cultured
• Collagen Type I (metabolism)
• Disease Models, Animal
• Extracellular Matrix (genetics, metabolism)
• Fibrosis
• Kidney (metabolism, pathology)
• Kidney Diseases (etiology, genetics, metabolism, pathology, prevention & control)
• Mice, Inbred C57BL
• Mice, Knockout
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Receptor, Platelet-Derived Growth Factor beta (metabolism)
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics, metabolism)
• Signal Transduction
• Time Factors
• Transforming Growth Factor beta (metabolism)
• Ureteral Obstruction (complications)