scholarly journals Activation of fibroblast growth factor-inducible 14 in the early phase of childhood IgA nephropathy

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258090
Author(s):  
Yuko Tezuka ◽  
Minenori Eguchi-Ishimae ◽  
Erina Ozaki ◽  
Toshiyuki Ito ◽  
Eiichi Ishii ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iga Nephropathy ◽  
Kidney Diseases ◽  
Early Stage ◽  
High Serum ◽  
Fibroblast Growth ◽  
Expression Array ◽  
Expression Arrays ◽  
Gene Expression Arrays

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Pediatric patients in Japan are diagnosed with IgAN at an early stage of the disease through annual urinary examinations. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) have various roles, including proinflammatory effects, and modulation of several kidney diseases; however, no reports have described their roles in pediatric IgAN. In this study, we performed pathological and immunohistochemical analyses of samples from 14 pediatric IgAN patients. Additionally, gene expression arrays of glomeruli by laser-captured microdissection were performed in hemi-nephrectomized high serum IgA (HIGA) mice, a model of IgA nephropathy, to determine the role of Fn14. Glomeruli with intense Fn14 deposition were observed in 80% of mild IgAN cases; however, most severe cases showed glomeruli with little or no Fn14 deposition. Fn14 deposition was not observed in obvious mesangial proliferation or the crescent region of glomeruli, but was detected strongly in the glomerular tuft, with an intact appearance. In HIGA mice, Fn14 deposition was observed mildly beginning at 11 weeks of age, and stronger Fn14 deposition was detected at 14 weeks of age. Expression array analysis indicated that Fn14 expression was higher in HIGA mice at 6 weeks of age, increased slightly at 11 weeks, and then decreased at 26 weeks when compared with controls at equivalent ages. These findings suggest that Fn14 signaling affects early lesions but not advanced lesions in patients with IgAN. Further study of the TWEAK/Fn14 pathway will contribute to our understanding of the progression of IgAN.

scholarly journals Localization of basic fibroblast growth factor mRNA (FGF-2 mRNA) in the uterus of mated and unmated gilts.

1996 ◽  
Vol 44 (11) ◽  
pp. 1289-1301 ◽  
Author(s):  
S Katsahambas ◽  
M T Hearn
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Early Stage ◽  
Vascular Endothelial Cell ◽  
Oligonucleotide Probes ◽  
Fibroblast Growth ◽  
Early Stages

In mated sows, the level of placental vascularization has a direct effect on fetal growth and litter birth weight. Vascularization of the endometrium and uterus under the control of various polypeptide growth factors is an important early stage in this process. Basic fibroblast growth factor (FGF-2), a polypeptide distributed throughout the mesodermal and neuroectodermal tissues of many species, is a vascular endothelial cell mitogen in vitro and has been implicated in neovascularization and wound healing in vivo. As part of our studies of the distribution of FGF-2 in uterine tissue and its role in placental development and embryo implantation, the localization and changes in the abundance of porcine FGF-2 mRNA in the uterus of mated and unmated gilts were investigated by in situ hybridization procedures. These procedures were based on the use of [alpha35S]-dATP-labeled oligonucleotide probes and a novel set of digoxigenin-labeled oligonucleotide probes generated by reverse transcriptase-polymerase chain reaction (RT-PCR) methods and anti-sense labeling strategies from the corresponding mRNA templates. With these in situ hybridization procedures, porcine FGF-2 mRNA was localized during the first 30 days of pregnancy to specific tissue areas in the porcine uterus comprising glandular and luminal epithelial cells and stromal cells of both the stratum functionalis and stratum basalis regions of the endometrium, and within the smooth muscle of myometrium and the associated blood vessels. However, no significant increase in the level of FGF-2 mRNA within these tissues was detected during these early stages of pregnancy or during the estrous cycle of unmated gilts. These distribution and abundance patterns are only partially compatible with other recent observations suggesting a possible role for changing levels of the mature polypeptide form of FGF-2 in the reproductive tract of sows during the early stages of pregnancy.

scholarly journals Role of fibroblast growth factor 21 in the early stage of NASH induced by methionine- and choline-deficient diet

2015 ◽  
Vol 1852 (7) ◽  
pp. 1242-1252 ◽  
Author(s):  
Naoki Tanaka ◽  
Shogo Takahashi ◽  
Yuan Zhang ◽  
Kristopher W. Krausz ◽  
Philip B. Smith ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Early Stage ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Deficient Diet

scholarly journals The Role of Mutant UDP-N-Acetyl-α-d-Galactosamine-Polypeptide N-Acetylgalactosaminyltransferase 3 in Regulating Serum Intact Fibroblast Growth Factor 23 and Matrix Extracellular Phosphoglycoprotein in Heritable Tumoral Calcinosis

2006 ◽  
Vol 91 (10) ◽  
pp. 4037-4042 ◽  
Author(s):  
Holly J. Garringer ◽  
Corinne Fisher ◽  
Tobias E. Larsson ◽  
Siobhan I. Davis ◽  
Daniel L. Koller ◽  
...  
Keyword(s):  
Growth Factor ◽  
Combination Therapy ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
High Serum ◽  
Biologically Active ◽  
Tumoral Calcinosis ◽  
Fibroblast Growth ◽  
Loss Of Function ◽  
Matrix Extracellular Phosphoglycoprotein

Abstract Context: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-α-d-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. Objective: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. Design, Setting, and Patients: We assessed the major biochemical defects and potential genes involved in patients with TC. Intervention: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. Results: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. Conclusions: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.

Sign in / Sign up

Export Citation Format

Share Document