Midkine in repair of the injured nervous system

Abstract

Midkine (MK) is a growth factor with neurotrophic and neurite outgrowth activities. It was expressed in the peri-ischaemic area in the acute phase of cerebral infarction in rat brains. Astrocytes were the origin of MK in this occasion. MK has been assessed in terms of its effects on neural injury. The administration of MK into the lateral ventricle immediately prior to ischaemia prevented cell death in the hippocampal CA1 neurons degenerated by transient forebrain ischaemia in gerbils. MK administration was also beneficial in rats with neural injury, especially after kainic acid-induced seizures. Gene therapy with mouse MK cDNA using an adenovirus was effective in reducing the cerebral infarction volume and in increasing the number of neuronal precursor cells in the subventricular zone of the rat brain. MK mRNA and MK protein were found in spinal cord motor neurons of the anterior horn in both the acute phase of sciatic nerve injury and 3 weeks later. MK immunoreactivity was also found in the proximal side of a sciatic nerve-injured site in sciatic nerve axons. MK receptors were expressed in Schwann cells after injury, suggesting crosstalk between axons and Schwann cells. MK was also present in nerve terminals and influenced ACh receptor clustering during neuromuscular development in Xenopus. Thus, MK may also be involved in reinforcing and maintaining the synapse. All these findings indicate the therapeutic potential of MK for promoting repair of the nervous system after injury.LINKED ARTICLESThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4

Midkine is overexpressed in acute pancreatitis and promotes the pancreatic recovery in L‐arginine‐induced acute pancreatitis in mice

“… Beyond the bioactivity on cartilage, the neurotrophic and neurite outgrowth activities of MK have also been widely reported. The study on MK knockout mice showed that the MK −/− mice has a regenerative delay of the axonal damage after freezing injury of the sciatic nerve . Furthermore, the role of MK in liver regeneration was investigated by Ochiai et al Their results show that MK is involved both in the inflammatory and reparative processes after partial hepatectomy and is beneficial for liver regeneration .…”

“…The study on MK knockout mice showed that the MK À/À mice has a regenerative delay of the axonal damage after freezing injury of the sciatic nerve. 29 Furthermore, the role of MK in liver regeneration was investigated by Ochiai et al Their results show that MK is involved both in the inflammatory and reparative processes after partial hepatectomy and is beneficial for liver regeneration. 30 In our study, the proliferative role of MK was also found in AP animal model, and rhMK presented a beneficial effect on the regeneration of exocrine pancreas after the acute inflammation.…”

The Therapeutic Effect of rhMK on Osteoarthritis in Mice, Induced by Destabilization of the Medial Meniscus

“…56,57) Another possible reason is that the rhMK promoted the retrieval of pathologic changed nervous system that was involved in the OA chronic pain. 2,3,5) Because beyond the bioactivity on cartilage, the neurotrophic and neurite outgrowth activities of MK have also been widely reported 22,23) . In addition, the study on Midkine knockout mice showed that the midkine (−/−) mice has a regenerative delay of the axonal damage after freezing injury of the sciatic nerve.…”

“…[20][21][22] MK and PTN not only play an important role in nervous system formation at the embryo stage 6) but also maintain its functions at the adult stage by protecting the injured neuron from apoptosis, preventing degradation of the peripheral and central nerves and promoting the regeneration and new synapses formation of the neuron. 23) MK also have the potency for cartilage regeneration: in vitro promoting the chondrocyte proliferation and cartilage related extracellular matrix expression 24,25) and in vivo increasing the thickness of joint cartilage.…”

Midkine: an emerging target of drug development for treatment of multiple diseases

“…Since midkine promotes the survival of injured neuronal cells, it has attracted attention from the viewpoint of therapy for various neuronal diseases. Pioneering research has been performed on ischemic brain injury (Yoshida et al ., ). Midkine is expressed around the infarcted area at the early stage of cerebral infarction.…”