Relle Manfred, Mayet Werner J, Strand Dennis, Brenner Walburgis, Galle Peter R, Schwarting Andreas
Department of Medicine, University of Mainz, Mainz, Germany.
J Nephrol. 2003 Nov-Dec;16(6):831-40.
Numerous data support the possible role of myeloblastin/proteinase 3 (PR3) in growth and differentiation of neutrophil granulocytes and certain monocyte subtypes. However, whether PR3 is expressed in non-myeloid cells remains a matter of debate even though recent studies clearly demonstrated its expression in endothelium, kidney epithelial cells and epithelial tumor cell lines.
To survey PR3 transcript presence in human tissues, we analyzed different human tissues by dot blot and northern blot using a cloned PR3-cDNA probe. To examine the physiological function of PR3 expression in non-myeloid cells, we constructed different recombinant retroviral vectors containing human PR3-cDNA variants and expressed them in tubular epithelial cells (TEC). Using an MTT-based proliferation assay, we determined the proliferation rate of PR3-transduced kidney cells.
The resulting expression pattern clearly indicated that PR3 transcripts are not only present in tissues known to harbor hematopoietic cells, but surprisingly PR3 was highly expressed in fetal organs including the kidney. The proliferation assay revealed that the growth rate of TEC transduced with native PR3 was significantly enhanced relative to non-transduced TEC.
The results supported our theory that PR3 can act as a growth factor in non-hematopoietic cells, analogous to its role in hematopoietic cells. The cells, recombinant vectors and methods described here serve as a basis to investigate PR3 function in cellular differentiation and proliferation, as well as its role in autoimmune diseases.
大量数据支持髓过氧化物酶/蛋白酶3（PR3）在中性粒细胞和某些单核细胞亚型的生长及分化中可能发挥的作用。然而，PR3是否在非髓系细胞中表达仍存在争议，尽管最近的研究明确证明其在内皮细胞、肾上皮细胞和上皮肿瘤细胞系中表达。
为了检测人组织中PR3转录本的存在情况，我们使用克隆的PR3 - cDNA探针通过斑点印迹和Northern印迹分析了不同的人组织。为了研究PR3在非髓系细胞中表达的生理功能，我们构建了包含人PR3 - cDNA变体的不同重组逆转录病毒载体，并在肾小管上皮细胞（TEC）中表达它们。使用基于MTT的增殖测定法，我们测定了PR3转导的肾细胞的增殖率。
所得的表达模式清楚地表明，PR3转录本不仅存在于已知含有造血细胞的组织中，而且令人惊讶的是，PR3在包括肾脏在内的胎儿器官中高度表达。增殖测定显示，与未转导的TEC相比，用天然PR3转导的TEC的生长速率显著提高。
结果支持了我们的理论，即PR3可以作为非造血细胞中的生长因子，类似于其在造血细胞中的作用。本文所述的细胞、重组载体和方法为研究PR3在细胞分化和增殖中的功能及其在自身免疫性疾病中的作用奠定了基础。
