Effect of Shenkang on renal fibrosis and activation of renal interstitial fibroblasts through the JAK2/STAT3 pathway.
BACKGROUND
Activation of renal fibroblasts is a critical mechanism in the process of renal fibrosis. As a commonly used herbal formula, Shenkang (SK) has been found to attenuate renal fibrosis and renal parenchyma destruction. However, the effect of SK on renal fibroblast activation in unilateral ureteral obstruction (UUO) mice and its molecular mechanism remain undetermined. The present study was performed to elucidate the effect of SK on renal fibroblast activation and renal fibrosis, as well as the potential underlying mechanism, in both NRK-49F cells and UUO mice.


METHODS
NRK-49F cells were stimulated with 10 ng/ml TGF-β1 for 48 h. After SK treatment, the CCK-8 method was used to evaluate cell viability. Thirty-six C57BL/6 mice were randomly divided into the sham group, UUO group, angiotensin receptor blocker (ARB) group, and SK high-, moderate- and low-dose groups. UUO was induced in mice except those in the sham group. Drugs were administered 1 day later. On the 13th day, the fractional anisotropy (FA) value was determined by MRI to evaluate the degree of renal fibrosis. After 14 days, serum indexes were assessed. Hematoxylin and eosin (HE) and Sirius red staining were used to observe pathological morphology and the degree of fibrosis of the affected kidney. Western blotting and PCR were used to assess the expression of related molecules in both cells and animals at the protein and gene levels.


RESULTS
Our results showed that SK reduced extracellular matrix (ECM) and α-smooth muscle actin (α-SMA) expression both in vitro and in vivo and attenuated renal fibrosis and the pathological lesion degree after UUO, suppressing JAK2/STAT3 activation. Furthermore, we found that SK regulated the JAK2/STAT3 pathway regulators peroxiredoxin 5 (Prdx5) in vitro and suppressor of cytokine signaling protein 1 (SOCS1) and SOCS3 in vivo.


CONCLUSIONS
These results indicated that SK inhibited fibroblast activation by regulating the JAK2/STAT3 pathway, which may be a mechanism underlying its protective action in renal fibrosis.
['Qin|Tianyu|T|', 'Wu|You|Y|', 'Liu|Tonghua|T|', 'Wu|Lili|L|']
D000199:Actins D000818:Animals D002460:Cell Line D056324:Diffusion Tensor Imaging D004353:Drug Evaluation, Preclinical D004365:Drugs, Chinese Herbal D005109:Extracellular Matrix D005347:Fibroblasts D005355:Fibrosis D053614:Janus Kinase 2 D007668:Kidney D008297:Male D008810:Mice, Inbred C57BL D009400:Nephrosclerosis D054464:Peroxiredoxins D008517:Phytotherapy D051381:Rats D050796:STAT3 Transcription Factor D000071222:Suppressor of Cytokine Signaling 1 Protein D000071223:Suppressor of Cytokine Signaling 3 Protein D053773:Transforming Growth Factor beta1 D014517:Ureteral Obstruction
Shenkang Renal fibrosis JAK2/STAT3 pathway Renal fibroblast activation UUO Chronic kidney disease