Midkine (MK) is a heparin-binding growth factor encoded by a retinoic acid responsive gene. To investigate the possible contribution of MK to genesis of colorectal carcinomas, an immunohistochemical examination of protein expression was conducted in sporadic and ulcerative colitis (UC)-associated tumors. MK expression significantly differed among normal mucosa, adenomas with low-grade dysplasia (LGD), adenomas with high-grade dysplasia (HGD) and invasive adenocarcinomas: MK expression was increased along with tumor progression. UC-associated lesions (regenerative mucosa of UC, UC-associated dysplasia and UC-associated adenocarcinoma) had similar variations. MK expression in UC-associated lesions was significantly higher than in normal mucosa, although there was no significant difference among UC-associated lesions. However, in UC-associated dysplasia, MK expression did not differ between the upper and lower halves, in contrast to adenoma with LGD and HGD, in which MK expression was significantly higher in the upper than lower halves, corresponding to cell proliferative zone. Furthermore, correlations with Ki-67 and single-strand DNA labeling, respectively, reflecting cellular proliferative activity and apoptosis, were noted in sporadic but not UC-associated lesions. These results suggest that MK is involved in genesis/development of sporadic colorectal tumors as well as of UC-associated tumors, but might contribute differently to genesis/development in these two types of tumors. 相似文献
Midkine (MK) is a multifunctional cytokine and heparin-binding growth factor with neurotrophic activity. MK and its receptor were examined for up to 14 days in a chemically injured rat muscle regeneration process caused by the injection of bupivacaine using immunohistochemical and Western blot analysis. Although MK immunoreactivity was not detectable in the mature uninjured skeletal muscle, MK was strongly detected in the regenerating muscle cells. MK immunoreactivity was observed in the myoblast-like cells and myotubes, which were desmin-positive cells, whereas it was not detectable in the surviving normal muscle fibers. Most myotubes labeling for desmin showed MK immunoreactivity 5-7days after the injury. However, MK immunoreactivity was not detected 14 days after the injury. Immunoreactivity of low-density lipoprotein receptor-related protein (LRP), a cell membrane receptor of MK, was detected in the regenerating muscle cells, whereas it was not detected in the normal adult skeletal muscle and surviving muscle. These findings suggested that MK was involved. MK may have a role for differentiation during skeletal muscle regeneration and may be taken up in an autocrine fashion with LRP. 相似文献
Background: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis.
Methods: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale.
Results: Our data showed that the serum MK concentration in ASD patients (mean ± SD, 11.51 ± 8.53 pg/ml) is significantly higher than healthy controls (mean ± SD, 6.19 ± 3.94 pg/ml) (p = 0.007).
Conclusions: According to these results, MK may play a role in ASD pathogenesis. 相似文献
Objectives: Midkine (MK) is involved in cell proliferation, differentiation, migration, and survival. In this study, we measured serum MK levels in rheumatoid arthritis (RA) and investigated the correlation of serum MK with RA disease activity. Expression and effect of MK in RA synovial tissue were also examined.
Methods: Serum MK and production of inflammatory mediators by rheumatoid synovial fibroblasts (RSFs) were measured by enzyme-linked immunosorbent assay. MK expression in synovial tissue was examined by immunohistochemistry. MK receptor expression was analyzed by RT-PCR and Western blotting.
Results: RA patients had a significantly higher serum MK level than healthy controls. In RA patients, the MK level was correlated with DAS28-ESR, disability index of the Health Assessment Questionnaire, and rheumatoid factor level. The serum MK level tended to be decreased by anti-TNF therapy. MK was expressed by synovial lining cells in RA synovial tissues and it enhanced the production of IL-6, IL-8, and CCL2 by RSFs. RSFs expressed LDL receptor-related protein 1, candidate receptor for MK.
Conclusions: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis. MK may have a role in the pathogenesis of RA via induction of inflammatory mediators. 相似文献