Dual roles of parathyroid hormone related protein in TGF-β1 signaling and fibronectin up-regulation in mesangial cells

Abstract

Little is known about the cross-talk between parathyroid hormone (PTH) related protein (PTHrP) and TGF-β1 in mesangial cells (MCs). Our results showed that PTHrP treatment (≤3 h) induced internalization of PTH1R (PTH/PTHrP receptor)–TβRII (TGF-β type 2 receptor) complex and suppressed TGF-β1-mediated Smad2/3 activation and fibronectin (FN) up-regulation. However, prolonged PTHrP treatment (12–48 h) failed to induce PTH1R–TβRII association and internalization. Total protein levels of PTH1R and TβRII were unaffected by PTHrP treatment. These results suggest that internalization of PTH1R and TβRII after short PTHrP treatment might not lead to their proteolytic destruction, allowing the receptors to be recycled back to the plasma membrane during prolonged PTHrP exposure. Receptor re-expression at the cell surface allows PTHrP to switch from its initial inhibitory effect to promote induction of FN. Our study thus demonstrates the dual roles of PTHrP on TGF-β1 signaling and FN up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for diabetic kidney disease (DKD).

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

“…In addition, there is evidence that PTH promotes fibrogenesis and collagen deposition [18,19]. PTH1R, a major receptor of PTH, has been found to be expressed in endothelial cells, fibroblasts and epithelial cells, which indicate the activating basis of application of PTH in skin tissue [20][21][22][23]. Therefore, we hypothesize that PTH might promote wound healing via multicellular stimulation and multilayer skin tissue repair.…”

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

“…Increasing evidence has shown that hyperglycemia promotes the expression of TGF-β1 in mesangial cells of the kidney and TGF-β1 promotes the expression of α-SMA, which are the biomarkers of fibrosis [ 22 , 23 ]. The accumulation of fibrotic factors of the renal is a critical factor in the mechanism responsible for the progression of renal fibrosis [ 24 – 27 ]. In our study, the glomerular fibrotic lesions and collagen accumulation were observed in DKD kidneys.…”

Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling

“…In glomerular mesangial cells (MCs), continuous expression of or incubation with PTHrP induces a proliferative effect (24 h) followed by hypertrophy at 72 h [10–12], and PTHrP-induced hypertrophic response is probably mediated by TGF-β1 [12]. Our previous study showed that PTHrP could induce fibronectin up-regulation in rat MCs [13]. However, whether PTHrP-induced extracellular matrix (ECM) up-regulation is mediated by TGF-β1 is still not clear.…”