The role of midkine and pleiotrophin in liver regeneration

Background/Purpose: We studied roles of two closely related heparin-binding growth factors, midkine (MK) and plieotrophin (PTN) in the processes of liver regeneration after partial hepatectomy. Methods: Liver regeneration was comparatively analyzed using mice deficient in the MK gene (Mdk), mice deficient in the pleiotrophin gene (Ptn) and wild-type mice. Results: Migration of neutrophils and macrophages to the liver 1-5 days after partial hepatectomy was suppressed in Mdk (-/-) mice. Liver damage as assessed by serum aspartate aminotransferase was also less severe in the deficient mice. On the other hand, cell growth in the liver was generally suppressed in the deficient mice 3-14 days after partial hepatectomy. The weight of the liver 7 and 14 days after partial hepatectomy was significantly less in Mdk (-/-) mice than wild-type mice. Very similar results were obtained using Ptn (-/-) mice except that a significant difference in the repaired liver weight was not observed between Ptn (-/-) mice and wild-type mice. Conclusions: MK and PTN are involved both in the inflammatory and reparative processes after partial hepatectomy, and as a whole are beneficial for liver regeneration.