PK2/PKR1 signaling pathway participates in geniposide protection against diabetic nephropathy in mice / 中国中药杂志

ABSTRACT

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.