Mika Kaakinen

University of Oulu · Biocenter Oulu

Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive le...

This study investigated two of the most commonly used CAD–CAM materials for patient-specific reconstruction in craniomaxillofacial surgery. The aim of this study was to access the biofilm formation of Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Escherichia coli on titanium and PEEK medical implant materials. Two titanium...

Dysfunctional and leaky blood vessels resulting from disruption of the endothelial cell (EC) barrier accompanies numerous diseases. The EC barrier is established through endothelial cell tight and adherens junctions. However, the expression patterning and precise contribution of different junctional proteins to the EC barrier is poorly understood....

Hypoxia plays an important regulatory role in the vasculature to adjust blood flow to meet metabolic requirements. At the level of gene transcription, the responses are mediated by hypoxia-inducible factor (HIF) the stability of which is controlled by the HIF prolyl 4-hydroxylase-2 (PHD2). In the lungs hypoxia results in vasoconstriction, however,...

The aim of this study was to assess the biofilm formation of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli on titanium implants with CAD-CAM tooling techniques. Twenty specimens of titanium were studied: Titanium grade 2 tooled with a Planmeca CAD-CAM milling device (TiGrade 2), Ti6Al4V grade 5 as it comes...

The pathogenesis of numerous diseases is characterised by disruption of the junctions that form the endothelial cell (EC) barrier, the composition of which may differ greatly between organs. However, the expression level variability and precise contribution of different junctional proteins is poorly understood. Here, we focus on organs with continu...

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of > 300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effe...

Vascular Endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in progression of diseases such as cancer and eye diseases. Inhibitors of SRC cytoplasmic tyrosine kinase have been applied to suppress tyrosine phosphorylation of VE-cadherin and the...

We critically evaluated the fetal microbiome concept in 44 neonates with placenta, amniotic fluid, and first-pass meconium samples. Placental histology showed no signs of inflammation. Meconium samples were more often bacterial culture positive after vaginal delivery. In next-generation sequencing of the bacterial 16S gene, before and after removal...

Background The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids ha...

Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. H...

Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. H...

Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. H...

The maintenance of fluid homeostasis is necessary for function of the neural retina; however, little is known about the significance of potential fluid management mechanisms. Here, we investigated angiopoietin-4 (Angpt4, also known as Ang3), a poorly characterized ligand for endothelial receptor tyrosine kinase Tie2, in mouse retina model. By using...

The development of tissue fibrosis is complex and at the present time, not fully understood. Fibrosis, neurodegeneration and cerebral angiomatosis (FINCA disease) have been described in patients with mutations in NHL repeat -containing protein 2 (NHLRC2). However, the molecular functions of NHLRC2 are uncharacterized. Herein, we identified putative...

Monitoring blood-brain barrier (BBB) opening is of great interest in terms of brain drug delivery in the treatment of brain lymphoma and maybe in the future in other diseases like dementia. A method involving BBB disruption (BBBD) by mannitol infusion has been developed in University of Portland, USA, and then exploited in Oulu University Hospital...

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary...

Caveolae and associated cavin and caveolins may govern myocardial function, together with responses to mechanical and ischaemic stresses. Abnormalities in these proteins are also implicated in different cardiovascular disorders. However, specific roles of the cavin-1 protein in cardiac and coronary responses to mechanical/metabolic perturbation rem...

Blue Rubber Bleb Nevus syndrome (Bean syndrome, BRBN) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations (VMs); gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with BRBN. Somatic mutations were also ide...

Toll-like receptor 9 (TLR9) is a cellular DNA-receptor widely expressed in cancers. We previously showed that synthetic and self-derived DNA fragments induce TLR9-mediated breast cancer cell invasion in vitro. We investigated here the invasive effects of two nuclease-resistant DNA fragments, a 9-mer hairpin, and a G-quadruplex DNA based on the huma...

Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of com...

Automated image analysis is demanded in cell biology and drug development research. The type of microscopy is one of the considerations in the trade-offs between experimental setup, image acquisition speed, molecular labelling, resolution and quality of images. In many cases, phase contrast imaging gets higher weights in this optimization. And it c...

Live cell imaging in 3D platforms is a highly informative approach to visualize cell function and it is becoming more commonly used for understanding cell behavior. Since these experiments typically generate large data sets their analysis manually would be very laborious and error prone. This has led to the necessity of automatic image analysis too...

Phase-contrast illumination is simple and most commonly used microscopic method to observe nonstained living cells. Automatic cell segmentation and motion analysis provide tools to analyze single cell motility in large cell populations. However, the challenge is to find a sophisticated method that is sufficiently accurate to generate reliable resul...

TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR...

The role of tumor stroma in regulation of breast cancer growth has been widely studied. However, the details on the type of heterocellular cross-talk between stromal and breast cancer cells (BCCs) are still poorly known. In the present study, in order to investigate the intercellular communication between human mesenchymal stromal cells (hMSCs) and...

We examine the distribution of gene products in skeletal myofibers, which are highly differentiated multinucleated cells exhibiting a specific cellular architecture. In situ hybridization studies of adult rat myofibers with a single nucleus infected with influenza virus suggested that the viral mRNA products were distributed beneath the sarcolemma...

Objective: The objective of this study was to validate the immunohistochemical assay for the diagnosis of nondystrophic myotonia and to provide full clarification of clinical disease to patients in whom basic genetic testing has failed to do so. Methods: An immunohistochemical assay of sarcolemmal chloride channel abundance using 2 different ClC...

We analyzed the existence of lipid bodies (LBs) in the fast twitch rat flexor digitorum brevis (FDB) myofibers and found that these structures were scarce. However, isolation procedure of the myofibers, heath shock, viral infection or the glycosylation inhibitor tunicamycin induced formation of the LBs, which were stationary structures flanking Z l...

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is shown to be a potential marker for poor prognosis in breast cancer, but the biology of TIMP-1 is only partially understood. In this study, TIMP-1 production was studied in a co-culture model of hormone-independent breast cancer cell lines and mesenchymal stem cells mimicking the stromal component...

We examined the distribution of selected raft proteins on the sarcolemma of skeletal myofibers and the role of cholesterol environment in the distribution. Immunofluorescence staining showed that flotillin-1 and influenza hemagglutinin exhibited rafts that located in the domains deficient of the dystrophin glycoprotein complex, but the distribution...

Transverse (T) tubules comprise a tortuous network inside the skeletal myofibers enclosing a distinct osmotic environment. Here we have examined whether the T tubules contain aquaporin type 4 (AQP4) water channels to mediate rapid transmembrane water flow. Separation of T tubular and sarcolemmal membranes by sucrose density gradient centrifugation...

We examined the progression of the WSN influenza virus infection in isolated, multinucleated rat skeletal myofibers. Contrary to mononucleated cells, the adsorbed virions showed markedly delayed entry kinetics. Viral budding occurred on the sarcolemma, but the hemagglutinin envelope glycoprotein matured inefficiently and was poorly cleaved. Compati...

We investigated the targeting of the gamma-actin isoform in skeletal myofibers. For this purpose we used expression vectors to produce green fluorescent protein (GFP-) as well as myc-tagged gamma-actin in rat flexor digitorum brevis myofibers. We found that the gamma-actin fusion proteins accumulated into Z discs but not beneath the sarcolemma. Ins...

The relationship between the endoplasmic reticulum (ER) and the sarcoplasmic reticulum (SR) of skeletal muscle cells has remained obscure. In this study, we found that ER- and SR-specific membrane proteins exhibited diverse solubility properties when extracted with mild detergents. Accordingly, the major SR-specific protein Ca(2+)-ATPase (SERCA) re...

The aquaporin 4 (AQP4) water channel is present on the sarcolemma of fast-twitch-type skeletal myofibres. We have examined the distribution of AQP4 in relation to sarcolemmal domain structure and found that AQP4 protein is not evenly distributed on the sarcolemma. Immunofluorescence staining of isolated single myofibres indicated a punctate stainin...

To evaluate low-intensity exercise training induced changes in the expression of dihydropyridine (DHP) and ryanodine (Ry) receptors both mRNA and protein levels were determined by quantitative RT-PCR and immunoblot analysis from gastrocnemius (GAS) and rectus femoris (RF) muscles of mice subjected to a 15-week aerobic exercise program. The level of...

Aquaporin-4 (AQP4) water channel is abundant at the sarcolemma of skeletal muscle and presumably plays a substantial role in adapting the rapid changes in fiber volume as well as osmotic pressure during repeated muscle contractions. In this paper we report on the expression of AQP4 and its correlation to the metabolic and functional development of...