Cellular Origin and Functional Relevance of Collagen I Production in the Kidney

Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow-derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal functi...

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Vydané v:	Journal of the American Society of Nephrology Ročník 29; číslo 7; s. 1859
Hlavní autori:	Buchtler, Simone, Grill, Alexandra, Hofmarksrichter, Stefanie, Stöckert, Petra, Schiechl-Brachner, Gabriela, Rodriguez Gomez, Manuel, Neumayer, Sophia, Schmidbauer, Kathrin, Talke, Yvonne, Klinkhammer, Barbara M, Boor, Peter, Medvinsky, Alexander, Renner, Kerstin, Castrop, Hayo, Mack, Matthias
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.07.2018
Predmet:	Acute Kidney Injury - etiology Acute Kidney Injury - metabolism Acute Kidney Injury - pathology Acute Kidney Injury - physiopathology Adenine Animals Bone Marrow Cells - metabolism Cell Lineage Collagen Type I - genetics Collagen Type I - metabolism Epithelial Cells - metabolism Female Fibroblasts - metabolism Fibrosis Glomerular Filtration Rate Hematopoiesis Kidney - pathology Kidney - physiopathology Kidney Tubules - cytology Mice Mice, Knockout Renal Insufficiency, Chronic - chemically induced Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Renal Insufficiency, Chronic - physiopathology Ureteral Obstruction - complications chronic kidney disease fibrosis interstitial fibrosis chronic renal failure immunology
ISSN:	1533-3450, 1533-3450
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Popis
Shrnutí:	Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow-derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear. We generated conditional cell type-specific collagen I knockout mice and used (reversible) unilateral ureteral obstruction and adenine-induced nephropathy to study renal fibrosis and function. In these mouse models, hematopoietic, bone marrow-derived cells contributed to 38%-50% of the overall deposition of collagen I in the kidney. The influence of fibrosis on renal function was dependent on the type of damage. In unilateral ureteral obstruction, collagen production by resident fibroblasts was essential to preserve renal function, whereas in the chronic model of adenine-induced nephropathy, collagen production was detrimental to renal function. Our data show that hematopoietic cells are a major source of collagen and that antifibrotic therapies need to be carefully considered depending on the type of disease and the underlying cause of fibrosis.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1533-3450 1533-3450
DOI:	10.1681/ASN.2018020138