Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte-derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN.

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Diabetic nephropathy (DN)2 is the most common and important chronic kidney disease and is the leading cause of end-stage kidney disease (ESKD) worldwide. The characteristic glomerular changes resulting from DN are thickening of the glomerular basement membrane (GBM) and expansion of the mesangial area caused by increased mesangial extracellular matrix (ECM). Mesangial cells (MCs) are the major source of ECM synthesis in diabetic glomeruli (1-3). Hyperglycemia, advanced glycation end products (AGEs), and transforming growth factor-␤ (TGF-␤) are implicated in the progression of DN by stimulating ECM production in MCs (4 -6). In addition, the phenotypic modulation and dedifferentiation of MCs, which are derived from mesenchymal cells, are key pathological events (7,8). MCs acquired phenotypes not only of activated smooth muscle cells but also of fibroblasts, and subsequently secrete excess ECM proteins.We previously reported that Smad1 is a direct transcriptional regulator of type IV collagen (COL4), a major component of increased mesangial ECM in DN, as well as other ECM proteins such as type I collagen (COL1), osteopontin, and ␣-smooth muscle actin (␣-SMA) (4, 9). The most critical feature of glomerulosclerosis is mesangial expansion, which is strongly correlated with decreased glomerular filtration rate (GFR) (10). Most importantly, we found that the glomerular expression levels of Smad1 are clearly correlated with the severities of mesangial matrix expansion in rodent DN (9, 11). Therefore, we have concluded that Smad1 plays a central role in the development of DN. However, we still lack mechanistic insight into how Smad1 is involved in phenotypic alteration of MCs and in the irreversible progression of DN. It is generally acknowledged that Smad1 transduces TGF-␤ signals and also transduces BMP signals through its receptors (12, 13). Although impairment of vascular wall integrity caused by mesangial matrix expansion leads to irreversible glomerulosclerosis, the molecular mechanisms underlying this irreversible change in the phenotypes of MCs in advanced DN are still unknown. We also demonstrated previously that a transcription factor, SRY-related HMG Box 9 (SOX9), is involved in the modulation of transcriptional enhancement of COL4 (14), but we still do not know how this influences the phenotypic alteration of MCs.It is well recognized that SOX9 is a cartilage-specific transcription factor; that is, the expression of SOX9 is required for

We report a case of hemopneumothorax secondary to multiple cavitary metastasis in the angiosarcoma of the scalp in an 86-year-old woman, who died of respiratory failure. At autopsy, multiple cavities were found in both lungs. Histologic specimen of the cavitary metastasis of the lung showed that tumor cells proliferated forming several tubular spaces and these tubular spaces seemed to communicate with the central cyst. These findings suggested that imperfect vessel-like structures of the cavitary metastasis are likely to break down and finally grow up to large thin-walled cavities.