RESUMO
Tubular epithelialmyofibroblast transdifferentiation (TEMT) is important in the development of chronic renal failure. The present study investigated whether hepatocyte growth factor (HGF) inhibits TEMT, and whether this function may be associated with the inhibition of angiotensin II (AngII) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Human HK2 kidney proximal tubular cells were divided into 4 groups and treated with AngII (1x106 M), HGF (8x103 M), AngII plus HGF or control conditions, followed by an assessment of apoptosis induction and the expression levels of αsmooth muscle actin (αSMA), which is a marker of TEMT. as well as the activation level of JAK2, phosphorylated (p)JAK2, STAT3 and pSTAT3 signaling pathways. In HK2 cells, αSMA mRNA and protein expression levels increased following treatment with AngII, however, decreased expression was observed following exposure to HGF. HGF counteracted the AngIIinduced increase in the expression of αSMA in HK2 cells. Similar expression profiles were observed for the phosphorylated forms of JAK2 and STAT3, indicating the possible involvement of this signaling pathway. The results demonstrated that treatment of cells with AngII was associated with the induction of apoptosis when compared with the control. By contrast, treatment with HGF attenuated AngIIinduced apoptosis. The results suggested that HGF may inhibit TEMT by inhibiting AngII through the JAK2/STAT3 signaling pathway in HK2 cells and HGF may prevent apoptosis induced by AngII. The present study provides a basis for understanding the mechanisms involved in the inhibition of TEMT by HGF, which requires further investigation.
Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Janus Quinase 2/metabolismo , Túbulos Renais/metabolismo , Miofibroblastos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , HumanosRESUMO
Several studies have shown that hepatocyte growth factor (HGF) ameliorates chronic renal failure, but its mechanism of action is unclear. This study was designed to test the delivery of HGF in the PCI-neo vector, using the 5/6 nephrectomized rat as a model for chronic renal failure, and to confirm that this protective function is associated with decreased protein expression of transforming growth factor-beta1 (TGF-ß1). Rats were randomly divided into the following groups: Control (untreated), PCI-neo (vector control), 5/6 nephrectomy, and PCI-neo-HGF. Rats were sacrificed at both the fifth and ninth week after 5/6 nephrectomy. Kidney specimens were used for pathological examination (hematoxylin-eosin staining), and detection of TGF-ß1 protein (Western blot and immunohistochemistry) expression. Blood urea nitrogen, serum creatinine, and 24-h urinary protein excretion (UPE) were increased, renal interstitium was seriously injured, and TGF-ß1 protein expression was elevated in 5/6 nephrectomized rats compared to control rats at either time point. Red blood cell and hemoglobin levels decreased in the ninth week after 5/6 nephrectomy. PCI-neo-HGF expression ameliorated the aforementioned changes and decreased TGF-ß1 expression, not only in the fifth week, but also in the ninth week after surgery. The process of renal injury in the 5/6 nephrectomized rat was consistent with that of chronic renal failure. The increase in TGF-ß1 expression was maintained after 5/6 nephrectomy. HGF relieved chronic renal failure, this protection was associated with down-regulation of TGF-ß1 protein expression, and the protective effects were long-term and stable after 5/6 nephrectomy.
Assuntos
Fator de Crescimento de Hepatócito/farmacologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Rim/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Western Blotting , Creatinina/sangue , Modelos Animais de Doenças , Regulação para Baixo , Contagem de Eritrócitos , Hemoglobinas/metabolismo , Imuno-Histoquímica , Rim/metabolismo , Rim/patologia , Masculino , Nefrectomia , Plasmídeos , Proteinúria , RatosRESUMO
OBJECTIVE: To analyze the correlation between the level of serum uric acid and the clinical and pathological features of IgA nephropathy. METHODS: Totally 148 patients diagnosed as IgA nephropathy by renal biopsy in our hospital from January 2007 to December 2010 were divided into hyperuricaemic group (41 cases) and non-hyperuricaemic group (107 cases) according to the level of serum uric acid. The clinical parameters and renal pathology grade were compared. RESULTS: There were significant differences between hyperuricaemic group and non-hyperuricaemic group in the incidences of hypertension (63.4% vs 38.3%), disease duration [(18.90 ± 10.12) months vs (9.46 ± 3.91) months] and body mass index [(22.81 ± 3.60) kg/m(2) vs (15.32 ± 2.54) kg/m(2)] (all P < 0.05), while no differences in age and sex (both P > 0.05). The blood urea nitrogen (BUN) [(8.93 ± 4.28) mmol/L vs (5.21 ± 2.18) mmol/L], creatinine (Cr) [(155.96 ± 107.72) µmol/L vs (79.52 ± 40.01) µmol/L], serum triglycerides [(2.11 ± 1.06) mmol/L vs (1.86 ± 1.20) mmol/L] and 24-hour urine protein amount [(4328.16 ± 1434.25) mg/24 h vs (2885.10 ± 1388.15) mg/24 h] were significantly different between the two groups (all P < 0.05). The percentage of Lee's grade I + II in hyperuricaemic group was 12.2%, and IV + V grade was 39.0%, while percentage of Lee's grade I + II in non-hyperuricaemic group was 25.2%, and IV + V grade was 16.9% (P < 0.05). Tubulointerstitial lesions (TIL) grade III + IV was more in hyperuricaemic group, which was 68.3%, while TIL grade II was more in non-hyperuricaemic group, which was 76.6%. Renal artery damage grade II + III was more in hyperuricaemic group, which was 73.2%, while renal artery damage grade 0 + I was more in non-hyperuricaemic group, which was 69.2%. CONCLUSIONS: The level of serum uric acid was related with 24-hour urine protein amount, blood pressure and kidney function in IgA nephropathy, and Lee's grade, TIL grade and renal artery damage grade were severe in hyperuricaemic group.