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Non-muscle myosin heavy chain 9-related disease (MYH9-RD) is an autosomal dominant disease caused by the mutations of the MYH9 gene encoding the non-muscle mysoin heavy chain ⅡA and leads to abnormal accumulation of myosin in cells. These further causes functional disorders of the blood, eye, ear, kidney, and liver systems. MYH9-RD displays heterogeneous kidney involvement and outcomes, but doctors still lack understandings of the mechanism and treatment strategies, owing to difficulty of conducting renal biopsies. Here, we report a case of MYH9-RD with tail fragments heterozygous mutation, which renal pathology is presented as glomerular minor lesion. Moreover, we reviewed related relevant to strengthen clinical diagnosis and understanding of MYH9-RD.

Aim Methods Results Conclusion Inflammation plays a critical role in the progression of diabetic nephropathy. Peroxisome proliferator‐activated receptor gamma (PPARγ) and its coactivator PPARγ coactivator‐1 alpha (PGC‐1α) enhance mitochondrial biogenesis and cellular energy metabolism but inhibit inflammation. However, the molecular mechanism through which these two proteins cooperate in the kidney remains unclear. The aim of the present study was to investigate this mechanism.HK‐2 human proximal tubular cells were stimulated by inflammatory factors, the expression of PPARγ and PGC‐1α were determined via reverse transcription‐quantitative polymerase chain reaction (PCR) and western blotting (WB), and DNA binding capacity was measured by an EMSA. Furthermore, db/db mice were used to establish a diabetic nephropathy model and were administered PPARγ and PGC‐1α activators. Kidney injury was evaluated microscopically, and the inflammatory response was assessed via WB, immunohistochemistry and immunofluorescence staining. Besides, HK‐2 cells were stimulated by high glucose and inflammatory factors with and without ZLN005 treatment, the expression of PPARγ, PGC‐1α, p‐p65 and p65 were determined via qPCR and WB.Our results revealed that both TNF‐α and IL‐1β significantly decreased PPARγ and PGC‐1 expression in vitro. Cytokines obviously decreased PPARγ DNA binding capacity. Moreover, we detected rapid activation of the NF‐κB pathway in the presence of TNF‐α or IL‐1β. PPARγ and PGC‐1α activators effectively protected against diabetic nephropathy and suppressed NF‐κB expression both in db/db mice and HK‐2 cells.PPARγ and its coactivator PGC‐1α actively participate in protecting against renal inflammation by regulating the NF‐κB pathway, which highlights their potential as therapeutic targets for renal diseases. [ABSTRACT FROM AUTHOR]

Background This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14–3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin–creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine. [ABSTRACT FROM AUTHOR]