Perspectives on the role of PTEN in diabetic nephropathy: an update.

Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.

S100A12 inhibits Streptococcus pneumoniae and aids in wound healing of corneal epithelial cells both in vitro and in vivo.

Streptococcus pneumoniae, a leading cause of corneal infections worldwide, are extremely aggressive despite antibiotic sensitivity and exhibit increased resistance towards antibiotics. Antimicrobial peptides are often considered as potent alternatives against antibiotic resistance and here we have investigated the possible roles of S100A12, a host defense peptide, in wound healing and S. pneumoniae infection. S100A12 significantly inhibited growth of S. pneumoniae by disruption of membrane integrity along with increased generation of reactive oxygen species. Additionally, S100A12 accelerated cell migration and wound closure in human corneal epithelial cells and in a murine corneal wound model by activation of EGFR and MAPK signaling pathways.

A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors. METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR. RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients. CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

microRNAs in Mycobacterial Infection: Modulation of Host Immune Response and Apoptotic Pathways.

Our current knowledge of mycobacterial infections in humans has progressively increased over the past few decades. The infection of Mycobacterium tuberculosis causes tuberculosis (TB) disease, which has reasoned for excessive morbidity and mortality worldwide, and has become a foremost issue of health problem globally. Mycobacterium leprae, another member of the family Mycobacteriaceae, is responsible for causing a chronic disease known as leprosy that mainly affects mucosa of the upper respiratory tract, skin, peripheral nerves, and eyes. Ample amount of existing data suggests that pathogenic mycobacteria have skilled in utilizing different mechanisms to escape or offset the host immune responses. They hijack the machinery of immune cells through the modulation of microRNAs (miRs), which regulate gene expression and immune responses of the host. Evidence shows that miRs have now gained considerable attention in the research, owing to their involvement in a broad range of inflammatory processes that are further implicated in the pathogenesis of several diseases. However, the knowledge of functions of miRs during mycobacterial infections remains limited. This review summarises recent findings of differential expression of miRs, which are used to good advantage by mycobacteria in offsetting host immune responses generated against them.

Arid5a Regulation and the Roles of Arid5a in the Inflammatory Response and Disease.

Abnormal gene expression patterns underlie many diseases that represent major public health concerns and robust therapeutic challenges. Posttranscriptional gene regulation by RNA-binding proteins (RBPs) is well-recognized, and the biological functions of RBPs have been implicated in many diseases, such as autoimmune diseases, inflammatory diseases, and cancer. However, a complete understanding of the regulation mediated by several RBPs is lacking. During the past few years, a novel role of AT-rich interactive domain-containing protein 5a (Arid5a) as an RBP is being investigated in the field of immunology owing to binding of Arid5a protein to the 3' untranslated region (UTR) of Il-6 mRNA. Indeed, Arid5a is a dynamic molecule because upon inflammation, it translocates to the cytoplasm and stabilizes a variety of inflammatory mRNA transcripts, including Il-6, Stat3, Ox40, T-bet, and IL-17-induced targets, and contributes to the inflammatory response and a variety of diseases. TLR4-activated NF-κB and MAPK pathways are involved in regulating Arid5a expression from synthesis to degradation, and even a slight alteration in these pathways can lead to intense production of inflammatory molecules, such as IL-6, which may further contribute to the development of inflammatory diseases such as sepsis and experimental autoimmune encephalomyelitis. This review highlights the regulation of the Arid5a expression and function. Additionally, recent findings on Arid5a are discussed to further our understanding of this molecule, which may be a promising therapeutic target for inflammatory diseases.