Transcription Factor Trps1 Promotes Tubular Cell Proliferation after Ischemia-Reperfusion Injury through cAMP-Specific 3',5'-Cyclic Phosphodiesterase 4D and AKT.

Trichorhinophalangeal 1 (Trps1) is a transcription factor essential for epithelial cell morphogenesis during kidney development, but the role of Trps1 in AKI induced by ischemia-reperfusion (I/R) remains unclear. Our study investigated Trps1 expression during kidney repair after acute I/R in rats and explored the molecular mechanisms by which Trps1 promotes renal tubular epithelial cell proliferation. Trps1 expression positively associated with the extent of renal repair after I/R injury. Compared with wild-type rats, rats with knockdown of Trps1 exhibited significantly delayed renal repair in the moderate I/R model, with lower GFR levels and more severe morphologic injury, whereas rats overexpressing Trps1 exhibited significantly accelerated renal repair after severe I/R injury. Additionally, knockdown of Trps1 inhibited and overexpression of Trps1 enhanced the proliferation of renal tubular epithelial cells in rats. Chromatin immunoprecipitation sequencing assays and RT-PCR revealed that Trps1 regulated cAMP-specific 3',5'-cyclic phosphodiesterase 4D (Pde4d) expression. Knockdown of Trps1 decreased the renal protein expression of Pde4d and phosphorylated Akt in rats, and dual luciferase analysis showed that Trps1 directly activated Pde4d transcription. Furthermore, knockdown of Pde4d or treatment with the phosphatidylinositol 3 kinase inhibitor wortmannin significantly inhibited Trps1-induced tubular cell proliferation in vitro Trps1 may promote tubular cell proliferation through the Pde4d/phosphatidylinositol 3 kinase/AKT signaling pathway, suggesting Trps1 as a potential therapeutic target for kidney repair after I/R injury.

Protective role of glycyrrhizin on experimental obstructive nephropat hy in rats / 第三军医大学学报

Objective　To investigate the protective role of glycyrrhizin on experimental obstructive nephropathy in rats. Methods 　The model of obstructive nephropathy was induced by unilateral uretera l ligation in rats and the animals were sacrificed at 12 h and 3,14,28,56 d resp ectively after operation. Specimens were taken from the cortex of kidney. In re nal stroma, routine morphological examinations and counts of karyocyte were made , the expression of collagen type Ⅰand type Ⅲ were also detected by immunohist ochemical staining,then, semi-quantified by EIG image analysis system. Results　 A progressive fibrosis was observed in renal stroma of the mod el. 12 h after operation, counts of karyocyte increased markedly i n renal stroma in groups of treatment and pretreatment with glycyrrhizin compar ed with that in sham-operation group（P<0.05）,and decreased distinctly compared with that in saline treated group（P<0.01）, but no significant di fference was found between treatment group and pretreatment group（P>0.05） ;3 d after operation, in group treated or pretreated with glycyrrhizin. The e xpression of collagen type Ⅰ increased markedly compared with that in sham-o peration group（P<0.01） in renal stroma, but decreased notably compare d with that in saline treated group（P<0.01）,while, there was not any diffe rence between treatment group and pretreatment group（P>0.05）. The expressi on of collagen type Ⅲ in renal stroma was almost the same as that of coll agen type Ⅰ. Conclusion　Glycyrrhizin has some therapeutical bu t no preventive effect to experimental obstructive nephropathy in rats.

Protective role of glycyrrhizin on experimental obstructive nephropat hy in rats / 第三军医大学学报

Objective　To investigate the protective role of glycyrrhizin on experimental obstructive nephropathy in rats. Methods 　The model of obstructive nephropathy was induced by unilateral uretera l ligation in rats and the animals were sacrificed at 12 h and 3,14,28,56 d resp ectively after operation. Specimens were taken from the cortex of kidney. In re nal stroma, routine morphological examinations and counts of karyocyte were made , the expression of collagen type Ⅰand type Ⅲ were also detected by immunohist ochemical staining,then, semi-quantified by EIG image analysis system. Results　 A progressive fibrosis was observed in renal stroma of the mod el. 12 h after operation, counts of karyocyte increased markedly i n renal stroma in groups of treatment and pretreatment with glycyrrhizin compar ed with that in sham-operation group（P<0.05）,and decreased distinctly compared with that in saline treated group（P<0.01）, but no significant di fference was found between treatment group and pretreatment group（P>0.05） ;3 d after operation, in group treated or pretreated with glycyrrhizin. The e xpression of collagen type Ⅰ increased markedly compared with that in sham-o peration group（P<0.01） in renal stroma, but decreased notably compare d with that in saline treated group（P<0.01）,while, there was not any diffe rence between treatment group and pretreatment group（P>0.05）. The expressi on of collagen type Ⅲ in renal stroma was almost the same as that of coll agen type Ⅰ. Conclusion　Glycyrrhizin has some therapeutical bu t no preventive effect to experimental obstructive nephropathy in rats.