Lack of PTH Accelerates Renal Fibrosis through Induction of Cellular Senescence and Upregulation of Senescence-associated Secretory Phenotype Molecules
Objective:This study aimed to investigate the effects of parathyroid hormone(Parathyroid hormone,PTH)deficiency on renal fibrosis and its underlying mechanisms.Methods:Two-month-old wild-type(WT)mice and PTH gene-deficient(PTH-/-)mice were used as models.Tissue histological staining,immunohistochemistry,Western blot,and qRT-PCR were performed to compare the differences in collagen deposition,cell proliferation,cellular senescence,and senescence-associated secretory phenotype(Senescence-as-sociated secretory phenotype,SASP)molecule expression in the renal tissue between the two groups of mice.Results:Compared with the WT group,PTH-/-mice showed significantly increased collagen deposition and expression of type I collagen mRNA in renal tissue.PTH deficiency also led to decreased expression of the antioxidant enzyme SOD1 in renal tissue,increased expression of the DNA dou-ble-strand break marker γ-H2A.X,and elevated levels of reactive oxygen species.Moreover,PTH-/-mice exhibited downregulation of the cell proliferation markers Ki67 and PCNA,increased expression of cell cycle arrest proteins p 16 and p53,and elevated senescence-asso-ciated β-galactosidase activity.In addition,SASP molecules IL-6,MMP3,and MMP13 were significantly upregulated in the renal tissue of PTH-/-mice.Conclusion:PTH deficiency can accelerate the process of renal fibrosis,likely through induction of oxidative stress and DNA damage in renal cells,inhibition of cell proliferation,exacerbation of cellular senescence,and upregulation of SASP molecule expression.This study sheds light on the important role of PTH in maintaining renal homeostasis.
NETL
NSTL
万方数据
