1,721,050 research outputs found
The folate way to T cell fate
No full textThe role of folate-dependent one carbon (1C) metabolism in CD4+ T cell polarization is incompletely understood. In this issue of Immunity, Sugiura et al. (2021) provide evidence that blocking the 1C metabolic enzyme MTHFD2 may curb pro-inflammatory CD4+ T cells, while redirecting them toward a regulatory T cell phenotype
Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists
No full textKidney disease is a frequent microvascular complication of both type 1 and type 2 diabetes. Historic trials have demonstrated that a tight glycaemic control is the most powerful approach to decrease the chances of developing diabetic nephropathy. However, having an HbA1c < 7% does not completely suppress the risk of kidney disease. The observed residual risk is likely ascribable to two phenomena: 1- the presence of risk factors and alterations additive to and independent of glycaemia, and 2- the activation of long-lasting imbalances by periods of exposure to uncontrolled glycemia, a phenomenon referred to as metabolic memory or legacy effect. Long-lasting oxidative stress, epigenetic alterations, cellular senescence, and the resulting chronic low-grade inflammation are all candidate mechanisms explaining the development of nephropathy despite proper control of risk factors. Recently, two classes of drugs, i.e. glucagon-like peptide (GLP) 1 receptor agonists (RA) and sodium-glucose transporter 2 inhibitors (SGLT-i) have changed this scenario. Indeed, cardiovascular outcome and other trials have clearly shown a renoprotective effect for these drugs, well-beyond their glucose-lowering properties. In this review, we summarize: 1- selected key trials and mechanisms underlying the development of diabetic kidney disease and 2- the results relative to renal endpoints in clinical trials of GLP-1 RA and SGLT-2i. Then, we briefly discuss some of the hypotheses posited to explain the marked renoprotective properties of these two classes, evidencing the still existing gaps in knowledge and proposing future directions to further implement the use of these powerful, disease-modifying drugs
The Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/LBP1
No full textThe Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/LBP1
No full textThe Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/LBP1
No full textA role for Id proteins in mammary gland physiology and tumorigenesis
No full textId helix-loop-helix (HLH) proteins are regulators of cell growth and differentiation in embryonic and adult tissues. They are members of the basic HLH family of transcription factors but lack a DNA binding domain. By binding to basic HLH transcription factors, Id proteins regulate gene expression. Id1 and Id3 have extensive sequence homology and similar patterns of expression during embryogenesis and in adult tissues. They are also expressed at high levels in the endothelial cells of tumor-infiltrating blood vessels, and breast tumors spontaneously arising in MMTV-neu mice demonstrate impaired angiogenesis when growing in an Id1- andor Id3-deficient background. These lesions are typically cystic with a small rim of viable tumor cells surrounding an acellular necrotic core. Id2 plays a critical role in breast differentiation and lactation. Id4 regulates BRCA1 expression and may be involved in hormone-dependent regulation of BRCA1 homeostasis. Thus, all four members of the Id protein family play pivotal roles in distinct aspects of normal and malignant breast biology, the subject of this review. © 2004 Elsevier Inc
Id4 messenger RNA and estrogen receptor expression: inverse correlation in human normal breast epithelium and carcinoma
No full textId (inhibitor of DNA binding) 4 is a member of the Id family of proteins (Id1-Id4), which function as dominant-negative regulators of basic helix-loop-helix transcription factors. Id factors are involved in numerous cell processes, including cell proliferation, differentiation, and tumorigenesis. We assessed the expression of Id4 messenger RNA (mRNA) in invasive mammary carcinoma from 31 patients, as well as in 21 cases of ductal carcinoma in situ, in 9 lymph node metastases, and in the morphologically normal epithelium adjacent to the carcinoma from the same subjects. In addition, we evaluated Id4 mRNA in atypical ductal hyperplasia from 5 other women and in normal breast tissue from yet another 5 women with no history of breast malignancy or atypia. The distribution of Id4 signal was assessed in relation to that of estrogen receptor (ER) in all samples and correlated with the Her-2 status of the carcinomas. Id4 mRNA was present in the normal ER-negative mammary epithelium in all cases; in contrast, the ER-positive cells present in the normal breast were Id4 negative. Id4 mRNA was not detected in atypical ductal hyperplasia, in 22 of the 23 cases of ductal carcinoma in situ, and in 27 of the 31 invasive carcinomas (P = .0008), all of which were ER positive. Conversely, 3 of the 31 invasive carcinomas were Id4 positive and ER negative. Only 1 ER-positive invasive carcinoma showed focal reactivity for Id4. The expression of Id4 in metastatic carcinoma paralleled that of the primary tumor. No correlation was apparent between Id4 and Her-2. Our data show that Id4 is constitutively expressed in the normal human mammary epithelium but is suppressed in ER-positive breast carcinomas and preneoplastic lesions. In contrast, ER-negative carcinomas appear to be Id4 positive. These results support a possible role of Id4 as a tumor suppressor factor in the human breast and suggest that the expression of Id4 in the mammary ductal epithelium may be regulated by estrogen. Further investigations are required to define the functions of Id4 in the human normal breast and in mammary neoplasia. © 2006 Elsevier Inc. All rights reserved
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