Background 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.

Methods 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.

Results 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.

Conclusions 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.

背景间质纤维化与慢性肾衰竭有关。除了成纤维细胞外，骨髓来源的细胞和肾小管上皮细胞也具有产生胶原蛋白的能力。然而，每种细胞类型产生的胶原蛋白量以及纤维化与肾功能的相关性尚不清楚。

方法我们培育了条件性细胞类型特异性 I 型胶原基因敲除小鼠，并使用（可逆性）单侧输尿管梗阻和腺嘌呤诱导的肾病来研究肾纤维化和功能。

结果在这些小鼠模型中，造血、骨髓来源的细胞占肾脏中 I 型胶原蛋白沉积总量的 38%–50%。纤维化对肾功能的影响取决于损伤的类型。在单侧输尿管梗阻中，常驻成纤维细胞产生的胶原蛋白对于保护肾功能至关重要，而在腺嘌呤诱发的肾病的慢性模型中，胶原蛋白的产生对肾功能有害。

结论我们的数据表明，造血细胞是胶原蛋白的主要来源，需要根据疾病类型和纤维化的根本原因仔细考虑抗纤维化治疗。