EGF stimulates müller glial proliferation via a BMP‐dependent mechanism

Müller glia, the major type of glia in the retina, are mitotically quiescent under normal conditions, though they can be stimulated to proliferate in some pathological states. Among these stimuli, EGF is known to be a potent mitogen for Müller glia. However, the signaling pathways required for EGF‐mediated proliferation of Müller glia are not clearly understood. In this study, postnatal day 12 (P12) or adult trp53^?/? mouse retinas were explanted and cultured in the presence of EGF to stimulate Müller glial proliferation. Treatment with signaling inhibitors showed that activation of both MEK/ERK1/2 and PI3K/AKT pathways is required for EGF‐induced proliferation of Müller glia. Interestingly, BMP/Smad1/5/8 activation downstream of PI3K/AKT signaling was also necessary for robust Müller glial proliferation, though activation of BMP/Smad1/5/8 signaling alone failed to stimulate their proliferation. In dissociated Müller glial culture, treatment with EGF induced the upregulation of Bmp7, and this upregulation was blocked significantly by co‐treatment with the BMP inhibitor dorsomorphin, suggesting that BMP/Smad1/5/8 activation is mediated at least in part by an autocrine mechanism in Müller glia. A better understanding of how BMP/Smad1/5/8 signaling is involved in glial proliferation may have important implications for proliferative disorders, as well as for retinal regeneration in mammalian retinas.     

Oral characteristics of a patient with Ekman-Westborg-Julin trait: a case history

This article presents the case of a Japanese woman who had Ekman-Westborg-Julin trait. She had general macrodontia with multituberculism, evagination of the premolar, single conical roots, shovel-shaped incisors, enamel hypoplasia, impacted tooth, dental crowding, and an open bite. The oral and general characteristics of this patient are described and include the histological and radiographic findings of the mandibular third molars. We suggest that the distinctive oral features with macrodontia of the permanent teeth, multituberculism, evagination, single conical roots, and impaction of the tooth could be defined as the Ekman-Westborg-Julin trait.     

Extracapillary proliferation and arteriolar hyalinosis are associated with long-term kidney survival in IgA nephropathy

Background

The Oxford classification of IgA nephropathy consists of four markers as prognosticators. We retrospectively examined the relevance of extracapillary proliferation involving cellular and fibrocellular crescents (Ex) and arteriolar hyalinosis (A) on the long-term outcome of renal function.

Methods

A total of 314 Japanese patients who were diagnosed with IgA nephropathy, with 12 months or more of follow-up period were included in this study. A total of 186 patients were with UP ≥ 0.5 g/day. Patients with diabetes mellitus or severe kidney injury (eGFR < 30 ml/min/1.73 m²) were excluded. The presence of Ex and A were scored 0 in the absence, and 1 in the presence, of each lesion. The end point was determined as a 50 % reduction in initial eGFR or end-stage renal disease defined as eGFR < 15 ml/min/1.73 m².

Results

In univariate analyses, the kidney survival rate was significantly lower in patients with Ex1 and A1 if UP ≥ 0.5 g/day. In the patients with UP < 0.5/day, none of the clinical and pathological parameters was determined as a risk factor. In the multivariate model including pathological parameters, Ex1 and A1 were independent risk factors for renal outcome if UP ≥ 0.5 g/day. In those patients treated with RAS-blocker or treated before introduction of methylprednisolone pulse therapy, Ex was the only independent risk factor. In multivariate analysis including clinical parameters, eGFR alone was a risk factor, due to strong correlation with other parameters.

Conclusion

Ex and A would be associated with the renal outcome of the patients with UP ≥ 0.5 g/day.

     

Effect of Morinda citrifolia fruit extract and its iridoid glycosides on blood fluidity

The aim of this study was to investigate the effect of Morinda citrifolia fruit on blood fluidity. M. citrifolia fruit extract (MCF-ext) was investigated for its influence on blood aggregation and fibrinolysis. MCF-ext inhibited polybrene-induced erythrocyte aggregation and thrombin activity. The fibrinolytic activity of MCF-ext, in the euglobulin lysis time test and fibrin plate assay, is reported here for the first time. One of the active compounds was an iridoid glycoside, asperulosidic acid. The results indicated that MCF-ext is a potentially useful health food which is capable of improving blood flow and preventing lifestyle-related diseases.     

Dynamic regulation and dysregulation of the water channel aquaporin-2: a common cause of and promising therapeutic target for water balance disorders

The human body is two-thirds water. The ability of ensuring the proper amount of water inside the body is essential for the survival of mammals. The key event for maintenance of body water balance is water reabsorption in the kidney collecting ducts, which is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and never allows permeation of ions or other small molecules. Under normal conditions, AQP2 is restricted within the cytoplasm of the collecting duct cells. However, when the body is dehydrated and needs to retain water, AQP2 relocates to the apical membrane, allowing water reabsorption from the urinary tubule into the cell. Its impairments result in various water balance disorders including diabetes insipidus, which is a disease characterized by a massive loss of water through the kidney, leading to severe dehydration in the body. Dysregulation of AQP2 is also a common cause of water retention and hyponatremia that exacerbate the prognosis of congestive heart failure and hepatic cirrhosis. Many studies have uncovered the regulation mechanisms of AQP2 at the single-molecule level, the whole-body level, and the clinical level. In clinical practice, urinary AQP2 is a useful marker for body water balance (hydration status). Moreover, AQP2 is now attracting considerable attention as a potential therapeutic target for water balance disorders which commonly occur in many diseases.