Role of Midkine in Glomerular and Tubulointerstitial Injuries

中期因子(Midkine，MK)是一种多潜能肝素结合生长因子，对中性粒细胞、巨噬细胞和神经元具有迁移促进活性。虽然MK的表达主要局限于肾脏的形成过程，但在病变肾脏的肾小管上皮细胞中也观察到MK的表达增强。对MK在肾小管间质损伤和肾小球损伤中的作用进行了研究。MK至少部分通过诱导MCP-I和MIP-2诱导炎性白细胞向肾小管间质趋化，MK参与了肾小管间质缺血损伤的加重。静脉注射MK反义寡核苷酸(ODN)后，MK主要分布于肾小管上皮细胞，MK在肾小管上皮细胞中的表达明显减少。这些结果表明，MK反义寡核苷酸有望成为治疗肾小管间质缺血损伤的新途径。

Midkine (MK) is a mutepotentioal heparin-binding growth factor with migration-promoting activity for neutrophils, macrophages and neurons. Although MK expression is mainly limited in the course of nephrogenesis, the enhanced expression of MK is also observed in the tubular epithelial cells in the diseased kidney. The role of MK in tubulointerstitial injuries as well as in glomerular injuries was studies. MK induces the chemotaxis of inflammatory leukocytes into the tubulointerstitium at least partially through the induction of MCP-I and MIP-2, and that MK contributes the aggravation of ischemia-induced tubulointerstitial damage.MK anti-sense oligonucleotide (ODN) distributes in the proximal tubular epithelial cells, which is the main part for de novo MK expression, after intravenous injection, and significantly reduced the expression of MK in the tubules. Consequently, MK antisense ODN successfully block the ischemic reperfusion injuries in the tubulointerstitium.These results strongly suggest that MK antisense ODN appears to be a candidate for the novel therapeutic approaches in ischemia-induced tubulointerstitial injuries.