Parathyroid hormone inhibits TGF-β/Smad signaling and extracellular matrix proteins upregulation in rat mesangial cells

Autor: Hong Yu, Fang-Fang Peng, Ze-Ling Xiao, Jian Zhou, Hong-Min Chen, Yan Chen, Bai-Fang Zhang
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
030232 urology & nephrology
Biophysics
Parathyroid hormone
Smad Proteins
SMAD
Protein Serine-Threonine Kinases
Biochemistry
Rats
Sprague-Dawley
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Transforming Growth Factor beta
Internal medicine
medicine
Animals
Humans
Phosphorylation
RNA
Small Interfering
Receptor
Molecular Biology
Receptor
Parathyroid Hormone
Type 1
Extracellular Matrix Proteins
biology
Chemistry
Receptor
Transforming Growth Factor-beta Type II
Cell Biology
Transforming growth factor beta
Endocytosis
Extracellular Matrix
Up-Regulation
Cell biology
Fibronectin
Glucose
030104 developmental biology
Endocrinology
Parathyroid Hormone
Mesangial Cells
biology.protein
RNA Interference
Signal transduction
Receptors
Transforming Growth Factor beta
Signal Transduction
Zdroj: Biochemical and Biophysical Research Communications. 478:1093-1098
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2016.08.073
Popis: Accumulation of glomerular matrix is a hallmark of diabetic nephropathy. TGF-β1 is a major cytokine mediating the production of various extracellular matrix (ECM) proteins. The aim of this study is to elucidate the effect of parathyroid hormone (PTH) on TGF-β1 and high glucose-induced upregulation of ECM proteins in primary mesangial cells from Sprague-Dawley rat. The results showed that PTH pretreatment prevented TGF-β1 and high glucose-induced Smad2/3 phosphorylation and consequent upregulation of fibronectin and type IV collagen within 4 h. The inhibitory effect of PTH is due to PTH1R activation, because knocking down PTH 1 receptor (PTH1R) by RNA interference reversed the inhibitory effect of PTH on TGF-β1 and high glucose-induced Smad2/3 phosphorylation and ECM upregulation. Furthermore, it is found that PTH1R associated with TGF-β type II receptor (TβR II) and both receptors internalized into the cytoplasm when mesangial cells were stimulated with PTH alone. The internalization of TβR II might reduce the amount of membrane TβR II, attenuate the sensitivity of mesangial cells to TGF-β1, and therefore inhibit Smad activation and ECM upregulation induced by TGF-β1 and high glucose. Further studies are needed to know whether the endocytic receptors are to be degraded or recycled, and evaluate the role of PTH in TGF-β1 signaling more comprehensively.
Databáze: OpenAIRE
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