Last update 01 Nov 2024

PAX4

Last update 01 Nov 2024

Basic Info

Synonyms

MODY9, paired box 4, Paired box protein Pax-4

+ [1]

Introduction

Plays an important role in the differentiation and development of pancreatic islet beta cells. Transcriptional repressor that binds to a common element in the glucagon, insulin and somatostatin promoters. Competes with PAX6 for this same promoter binding site. Isoform 2 appears to be a dominant negative form antagonizing PAX4 transcriptional activity.

Drugs associated with PAX4

JAG-301

Target

PAX4

Mechanism

PAX4 modulators [+1]

Active Org.

Jaguar Gene Therapy LLCStartup

Originator Org.

Jaguar Gene Therapy LLCStartup

Active Indication

Diabetes Mellitus, Type 1

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PAX4

100 Translational Medicine associated with PAX4

0 Patents (Medical) associated with PAX4

420

Literatures (Medical) associated with PAX4

01 Dec 2024·Molecular Biology Reports

Gene methylation in diabetic rats treated with an extract

Article

Author: Bahrami, Gholamreza ; Khazayel, Saeed ; Bahrami, MohammadTaher ; Javid, Hadis ; Miraghaee, Seyed Shahram ; Sajadimajd, Soraya ; Mohammadi, Bahareh

BACKGROUNDDiabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic β-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the β-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract.METHODS AND RESULTSStreptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes.CONCLUSIONThe results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.

01 Oct 2024·Journal of Endocrinology

Dual PPAR-a/g enhances beta cell identity, preserving islet structure in HF-fed mice

Article

Author: Fernandes-da-Silva, Aline ; Silva-Veiga, Flávia Maria ; Souza-Mello, Vanessa ; Mandarim-de-Lacerda, Carlos Alberto ; Miranda, Rosiane Aparecida ; Santana-Oliveira, Daiana Araujo ; Souza-Tavares, Henrique

The pancreas suffers from lipotoxicity, which threatens the survival of pancreatic islets. Dual PPAR-alpha(a)/gamma(g) agonism is a promising method for treating type 2 diabetes. This study evaluated the effects of single PPAR-a and PPAR-g or their combined activation on pancreatic islet remodeling, beta-cell proliferation, identity, and maintenance in an experimental obesity model. Fifty three-month-old mice, randomly divided to receive the control (C) or high-fat (HF) diet for ten weeks, were then redivided for a four-week treatment: C, HF, HF-a (received the PPAR-a agonist), HF-g (PPAR-g agonist pioglitazone), and HF-d (PPAR-a/g agonists). The HF group was overweight, had oral glucose intolerance, showed a proinflammatory adipokine profile, exhibited increased alpha and beta cell masses, and islet gene expression compatible with compromised beta cell proliferation and favored dedifferentiation. All treatments reduced body weight, mitigated oral glucose intolerance, and produced an anti-inflammatory adipokine profile, which rescued islet cytoarchitecture, and beta cell function. Principal component analysis (PCA) revealed a shift in the antiapoptotic gene Bcl2 and beta cell proliferation genes (Pax4 and Neurog3) in HF-a. Conversely, HF-g and HF-d benefited from the upregulation of genes related to beta cell function (Fgf21, Glut2, and Glp1r), identity, and maintenance (Pdx1, Neurod1, Mafa, and Nkx6.1). The HF mice were glucose intolerant, showing islet hypertrophy and low beta cell identity-related genes. In contrast, PPAR activation rescued islet structure, and PCA showed that the PPAR-a/g combination was the most effective treatment because it favored beta cell function, identity, and maintenance-related genes, halting the T2DM spectrum in diet-induced obese mice.

05 Aug 2024·Journal of Cell Biology

Proteasome gene expression is controlled by coordinated functions of multiple transcription factors

Article

Author: Nahar, Asrafun ; Kasiviswanathan, Dharanibalan ; Alexandrovich, Dina ; Mandel-Gutfreund, Yael ; Shemer, Shenhav ; Park, Soyeon ; Tropp, Nadav ; Gilda, Jennifer E ; Gilinski, Tamar ; Lahav, Tamar

Proteasome activity is crucial for cellular integrity, but how tissues adjust proteasome content in response to catabolic stimuli is uncertain. Here, we demonstrate that transcriptional coordination by multiple transcription factors is required to increase proteasome content and activate proteolysis in catabolic states. Using denervated mouse muscle as a model system for accelerated proteolysis in vivo, we reveal that a two-phase transcriptional program activates genes encoding proteasome subunits and assembly chaperones to boost an increase in proteasome content. Initially, gene induction is necessary to maintain basal proteasome levels, and in a more delayed phase (7–10 days after denervation), it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and α-PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and α-PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g., type-2 diabetes, cancer).

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PAX4

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