[Effects of salidroside on tubular epithelial to myofibroblast transition under cobaltous chloride induced hypoxic status].
OBJECTIVE
To investigate the effect and possible mechanism of salidroside on the transdifferentiation of normal rat kidney tubular epithelia cells (NRK52E) under cobaltous chloride (Co) induced hypoxic status.


METHODS
Cultured NRK52E cells were divided into control group, Co group and Co plus salidroside treatment groups at a dosage of 10 micromol/L, 50 micromol/L, and 100 micromol/L. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of oxygen homeostasis was measured as a marker of hypoxic status. Morphologic alteration of cells was observed by inverted phase contrast microscope. The expression of alpha-SMA in NRK52E cells was detected by fluorescent immunocytochemistry (FICC) and immunohistochemistry (IHC). The alpha-SMA and TGF-beta1 mRNA were assessed using reverse transcription-polymerase chain reaction (RT-PCR). The expressions of HIF-1alpha and alpha-SMA protein were detected by Western blot analyses. The enzyme-linked immunosorbent assay was performed to detect collagen I (Col-I) and fibronectin (FN) in the supernatant.


RESULTS
The expression of HIF-1alpha in NRK52E cells was induced by 100 micromol/L of Co in vitro. Co induced transdifferentiation of NRK52E cells, showing fibroblast-like in morphology. Salidroside partly blocked morphologic transformation of tubular epithelial cells. Salidroside decreased the expressions of alpha-SMA protein and mRNA and TGF-beta1 mRNA significantly (P < 0.05), although they were still higher than the controls (P <0 .05). Salidroside, especially in high dosage, inhibited the increase in Col-I and FN induced by Co (P < 0.05).


CONCLUSIONS
Hypoxia can induce tubular epithelial-myofibroblast transdifferentiation (TEMT). Salidroside improves Co-induced hypoxic status and inhibits TEMT possibly through reducing Col I and FN in NRK52E cells.
Zhang
Lei
L
Department of Nephrology , West China Hospital , Sichuan University, Chengdu, China.
Xie
Xi-Sheng
XS
Li
Fei-Yan
FY
Zhang
He-Ping
HP
Liu
Chang
C
Fan
Jun-Ming
JM
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D003035:Cobalt / Q000009:adverse effects; D004847:Epithelial Cells / Q000737:chemistry*; D005960:Glucosides / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology*; D058628:Myofibroblasts / Q000166:cytology*; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D029771:Rhodiola / Q000737:chemistry
D005960:Glucosides; D010636:Phenols; D003035:Cobalt; C018021:cobaltous chloride; C009172:rhodioloside