LMX1B

Recent demographic studies predict there will be a considerable increase in the number of elderly people within the next few decades. Aging has been recognized as one of the main risk factors for the world's most prevalent diseases such as neurodegenerative disorders, cancer, cardiovascular disease, and metabolic diseases. During the process of aging, a gradual loss of tissue volume and organ function is observed, which is partially caused by replicative senescence. The capacity of cellular proliferation and replicative senescence is tightly regulated by their telomere length...

INTRODUCTION: Neurological diseases, including Alzheimer's, Parkinson's diseases, and brain cancers, are reportedly caused by genetic aberration and cellular malfunction. Herbs with bioactive compounds that have anti-oxidant effects such as cordyceps and turmeric, are of interest to clinical applications due to their minimal adverse effects. The aim of study is to develop the nanoencapsulated cordyceps and turmeric extracts and investigate their capability to enhance the biological activity and improve neuronal function...

Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression...

The podocyte is a specialized cell type critically involved in maintaining the selective filtration barrier of the kidney. Podocytes are primary or secondary targets for a multitude of kidney diseases. Despite intense investigation, the transcriptome and proteome of human podocytes remain incompletely characterized. Here, we analyzed publicly available RNA-Seq data from human kidneys (n = 85) to computationally identify potential novel podocyte markers. For confirmation, we used an online histology resource followed by in-house staining of human kidneys and biochemical fractionation of glomeruli...

The spectra of underlying genetic variants for various clinical entities including focal segmental glomerulosclerosis (FSGS) vary among different populations. Here we described the clinical and genetic characteristics of biopsy-proven FSGS patients in Thailand. Patients with FSGS pathology, without secondary causes, were included in our study. Clinical laboratory and pathological data were collected. Whole-exome sequencing (WES) was subsequently performed. 53 unrelated FSGS patients were recruited. 35 patients were adults (66...

Mammalian digit tip regeneration is linked to the presence of nail tissue, but a nail-explicit model is missing. Here, we report that nail-less double-ventral digits of ΔLARM1/2 mutants that lack limb-specific Lmx1b enhancers fail to regenerate. To separate the nail's effect from the lack of dorsoventral (DV) polarity, we also interrogate double-dorsal double-nail digits and show that they regenerate. Thus, DV polarity is not a prerequisite for regeneration, and the nail requirement is supported. Transcriptomic comparison between wild-type and non-regenerative ΔLARM1/2 mutant blastemas reveals differential upregulation of vascularization and connective tissue functional signatures in wild type versus upregulation of inflammation in the mutant...

A reoccurring issue in neuroepigenomic studies, especially in the context of neurodegenerative disease, is the use of (heterogeneous) bulk tissue, which generates noise during epigenetic profiling. A workable solution to this issue is to quantify epigenetic patterns in individually isolated neuronal cells using laser capture microdissection (LCM). For this purpose, we established a novel approach for targeted DNA methylation profiling of individual genes that relies on a combination of LCM and limiting dilution bisulfite pyrosequencing (LDBSP)...

Here, we ask why the nail base is essential for mammalian digit tip regeneration, focusing on the inductive nail mesenchyme. We identify a transcriptional signature for these cells that includes Lmx1b and show that the Lmx1b-expressing nail mesenchyme is essential for blastema formation. We use a combination of Lmx1bCreERT2-based lineage-tracing and single-cell transcriptional analyses to show that the nail mesenchyme contributes cells for two pro-regenerative mechanisms. One group of cells maintains their identity and regenerates the new nail mesenchyme...

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder caused by a mutation in LIM-homeodomain transcription factor 1-beta (LMX1B) and characterized by nail dystrophy, skeletal changes, glaucoma, and kidney disease with up to 30% of patients progressing to kidney failure. Autoimmune diseases, including thyroid disease, have been reported previously in patients with NPS. CASE-DIAGNOSIS/TREATMENT: We report the case of a pediatric patient with NPS with kidney failure, hypothyroidism, and type 1 diabetes mellitus...

The mouse digit tip regenerates following amputation. How the regenerate is patterned is unknown, but a long-standing hypothesis proposes developmental patterning mechanisms are re-used during regeneration. The digit tip bone exhibits dorsal-ventral (DV) polarity, so we focus on En1 and Lmx1b, two factors necessary for DV patterning during limb development. We investigate whether they are re-expressed during regeneration in a developmental-like pattern and whether they direct DV morphology of the regenerate...

Rationale: Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disease (LSD) caused by mutations in NPC1 or NPC2 genes. Mutations result in abnormal cholesterol trafficking, which is manifested by abnormal cholesterol and glycosphingolipid accumulation in lysosomes of various cells. Presenting Concerns of the Patient: The patient had a history of hyperlipidemia, hypertension, depression, and elevated alkaline phosphatase and initially presented for a workup regarding chronic kidney disease stage G3b/A3 with proteinuria of 1...

The smoothened sonic hedgehog (Smo-Shh) pathway is one mechanism that influences neurogenesis, including brain cell differentiation and development during childhood. Shh signaling dysregulation leads to decreased target gene transcription, which contributes to increased neuronal excitation, apoptosis, and neurodegeneration, eventually leading to neurological deficits. Neuropsychiatric disorders such as OCD and related neurological dysfunctions are characterized by neurotransmitter imbalance, neuroinflammation, oxidative stress, and impaired neurogenesis, disturbing the cortico-striato-thalamo-cortical (CSTC) link neuronal network...

BACKGROUND: Osteolysis is one of the most common problems that occurs after total hip and knee arthroplasty and has recently become a significant problem after total ankle arthroplasty (TAA). In this study, we investigated the role of LIM homeobox transcription factor 1-β (Lmx1b) in osteoclast differentiation. By evaluating the expression profiles associated with osteolysis following TAA treatment, Lmx1b was found to be differentially expressed in patients with osteolysis after TAA. METHODS: To identify the important genes associated with osteolysis after TAA, RNA sequencing was performed by analyzing 8 patient samples: 5 primary TAA samples (control group) and 3 TAA samples revised for flexion instability (osteolysis group)...

Osteoarthritis (OA), a chronic degenerative joint disease, always occurred in the aging population. There is evidence suggests that chondrocytes' survival, inflammation, and apoptosis play critical roles in OA pathogenesis. LMX1B has been shown to be involved in antiosteogenic function in early patterning of the calvaria. However, the role and mechanism of LMX1B in OA is not unknown. The present study observed that LMX1B was highly expressed in OA patients compared with normal patients. Besides, we found that IL-1 β increased LMX1B mRNA and protein expression in SW1353 and C28/I2 chondrocytes...

Neuropeptide S (NPS) increases wakefulness. A small number of neurons in the brainstem express Nps. These neurons are located in or near the parabrachial nucleus (PB), but we know very little about their ontogeny, connectivity, and function. To identify Nps-expressing neurons within the molecular framework of the PB region, we used in situ hybridization, immunofluorescence, and Cre-reporter labeling in mice. The primary concentration of Nps-expressing neurons borders the lateral lemniscus at far-rostral levels of the lateral PB...

Epidemiological studies have shown that prenatal triphenyl phosphate (TPhP) exposure is related to abnormal neurobehavior in children. However, the neurodevelopmental toxicity of TPhP in mammals is limited. To study the neurodevelopmental toxicity of TPhP in mammals and investigate the underlying mechanism, we used a mouse intrauterine TPhP exposure model. We measured the inflammatory factors (IL-6, TNFα) and NFκB levels, and tryptophan metabolism in placentae, detected the fetal brain transcriptome, hippocampal neuron development and neurobehavioral in the male offspring...

In humans and rats, aging is associated with a progressive deterioration of spatial learning and memory. These functional alterations are correlated with morphological and molecular changes in the hippocampus. Here, we assessed age-related changes in DNA methylation (DNAm) landscape in the rat hippocampus and the correlation of spatial memory with hippocampal DNAm age in 2.6 months and 26.6 months old rats. Spatial memory performance was assessed with the Barnes maze test. In order to evaluate learning ability as well as spatial memory retention, we assessed the time spent by animals in goal sector 1 (GS1) and 3 (GS3) when the escape box was removed...

Prostate cancer (PCa) is the most common cancer affecting men, with increasing global mortality and morbidity rates. Despite the progress in the diagnosis and treatment of PCa, patient outcomes remain poor, and novel therapeutic targets for PCa are urgently needed. Recently, circular RNAs (circRNAs) have been studied in-depth as potential biomarkers for many diseases. In this study, circRNA microarrays using four pairs of PCa tissues were utilized to show that circGFRA1 was upregulated in PCa tumor tissues...

Neuronal programming by forced expression of transcription factors (TFs) holds promise for clinical applications of regenerative medicine. However, the mechanisms by which TFs coordinate their activities on the genome and control distinct neuronal fates remain obscure. Using direct neuronal programming of embryonic stem cells, we dissected the contribution of a series of TFs to specific neuronal regulatory programs. We deconstructed the Ascl1-Lmx1b-Foxa2-Pet1 TF combination that has been shown to generate serotonergic neurons and found that stepwise addition of TFs to Ascl1 canalizes the neuronal fate into a diffuse monoaminergic fate...

Nail-patella syndrome (NPS, OMIM #161200) is a rare autosomal dominant disorder with symptoms from many different parts of the body, including nails, knees, elbows, pelvis, kidneys and eyes. It is caused by truncating variants in the LMX1B gene, which encodes a transcription factor with important roles during embryonic development, including dorsoventral patterning of the limbs. To our knowledge, inversions disrupting the LMX1B gene have not been reported. Here, we report a family with an inversion disrupting the LMX1B gene in five affected family members with mild but variable clinical features of NPS...