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P311 promotes renal fibrosis via TGFβ1/Smad signaling.

Yao Z, Yang S, He W, Li L, Xu R, Zhang X, Li H, Zhan R, Sun W, Tan J, Zhou J, Luo G, Wu J - Sci Rep (2015)

Bottom Line: We previously observed that P311 is highly expressed in skin hypertrophic scars.The interstitial deposition of collagen, α-SMA and TGF-β1 expression, and macrophage infiltration were dramatically decreased when P311 was knocked out.In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.

ABSTRACT
P311, a gene that was identified in 1993, has been found to have diverse biological functions in processes such as cell proliferation, migration and differentiation. However, its role in fibrosis is unknown. We previously observed that P311 is highly expressed in skin hypertrophic scars. In this study, P311 over-expression was detected in a subset of tubular epithelial cells in clinical biopsy specimens of renal fibrosis; this over-expression, was found concurrent with α-smooth muscle actin (α-SMA) and transforming growth factor beta1 (TGFβ1) expression. Subsequently, these results were verified in a mouse experimental renal fibrosis model induced by unilateral ureteral obstruction. The interstitial deposition of collagen, α-SMA and TGF-β1 expression, and macrophage infiltration were dramatically decreased when P311 was knocked out. Moreover, TGFβ/Smad signaling had a critical effect on the promotion of renal fibrosis by P311. In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.

No MeSH data available.


Related in: MedlinePlus

P311 might be involved in macrophage infiltration in UUO mice.(A) Representative F480-stained sections of UUO kidneys from P311+/+ (n = 6) and P311−/− (n = 6) mice. Black arrowhead indicates the F480-positive cells. Bottom panel: negative controls for the immunohistochemical staining of F480 on the obstructed kidneys from both P311+/+ and P311−/− mice. (B) The graph represents the total number of F480-positive sections from five contiguous high-powered fields per kidney section. (A) and (B) are representative of at least three similar experiments. Scale bar: 100 μm. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01.
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f7: P311 might be involved in macrophage infiltration in UUO mice.(A) Representative F480-stained sections of UUO kidneys from P311+/+ (n = 6) and P311−/− (n = 6) mice. Black arrowhead indicates the F480-positive cells. Bottom panel: negative controls for the immunohistochemical staining of F480 on the obstructed kidneys from both P311+/+ and P311−/− mice. (B) The graph represents the total number of F480-positive sections from five contiguous high-powered fields per kidney section. (A) and (B) are representative of at least three similar experiments. Scale bar: 100 μm. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01.

Mentions: Fibrosis is the final, common pathological outcome of chronic inflammatory reactions induced by various stimuli, including tissue injury, chronic infections, autoimmune reactions, allergic responses, chemical insults and radiation26. Macrophages can synthesize TGF-β to activate fibrogenic cascades27. Therefore, we examined whether P311 regulates macrophage infiltration. We used an anti-F480 antibody to detect macrophage infiltration. Immunohistochemical staining revealed few F480-positive cells in the renal interstitium of mice in the Sham groups (data not shown). The number of F480-positive cells were significantly higher in the peritubular areas of obstructed kidneys from P311+/+ and P311−/− mice. However, the number of F480-positive cells was much higher in obstructed kidneys from P311+/+ mice (256) compared to P311−/− mice (197) (Fig. 7A,B, P = 0.005). Therefore, P311 might be involved in macrophage recruitment to obstructed kidneys.


P311 promotes renal fibrosis via TGFβ1/Smad signaling.

Yao Z, Yang S, He W, Li L, Xu R, Zhang X, Li H, Zhan R, Sun W, Tan J, Zhou J, Luo G, Wu J - Sci Rep (2015)

P311 might be involved in macrophage infiltration in UUO mice.(A) Representative F480-stained sections of UUO kidneys from P311+/+ (n = 6) and P311−/− (n = 6) mice. Black arrowhead indicates the F480-positive cells. Bottom panel: negative controls for the immunohistochemical staining of F480 on the obstructed kidneys from both P311+/+ and P311−/− mice. (B) The graph represents the total number of F480-positive sections from five contiguous high-powered fields per kidney section. (A) and (B) are representative of at least three similar experiments. Scale bar: 100 μm. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663757&req=5

f7: P311 might be involved in macrophage infiltration in UUO mice.(A) Representative F480-stained sections of UUO kidneys from P311+/+ (n = 6) and P311−/− (n = 6) mice. Black arrowhead indicates the F480-positive cells. Bottom panel: negative controls for the immunohistochemical staining of F480 on the obstructed kidneys from both P311+/+ and P311−/− mice. (B) The graph represents the total number of F480-positive sections from five contiguous high-powered fields per kidney section. (A) and (B) are representative of at least three similar experiments. Scale bar: 100 μm. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01.
Mentions: Fibrosis is the final, common pathological outcome of chronic inflammatory reactions induced by various stimuli, including tissue injury, chronic infections, autoimmune reactions, allergic responses, chemical insults and radiation26. Macrophages can synthesize TGF-β to activate fibrogenic cascades27. Therefore, we examined whether P311 regulates macrophage infiltration. We used an anti-F480 antibody to detect macrophage infiltration. Immunohistochemical staining revealed few F480-positive cells in the renal interstitium of mice in the Sham groups (data not shown). The number of F480-positive cells were significantly higher in the peritubular areas of obstructed kidneys from P311+/+ and P311−/− mice. However, the number of F480-positive cells was much higher in obstructed kidneys from P311+/+ mice (256) compared to P311−/− mice (197) (Fig. 7A,B, P = 0.005). Therefore, P311 might be involved in macrophage recruitment to obstructed kidneys.

Bottom Line: We previously observed that P311 is highly expressed in skin hypertrophic scars.The interstitial deposition of collagen, α-SMA and TGF-β1 expression, and macrophage infiltration were dramatically decreased when P311 was knocked out.In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.

ABSTRACT
P311, a gene that was identified in 1993, has been found to have diverse biological functions in processes such as cell proliferation, migration and differentiation. However, its role in fibrosis is unknown. We previously observed that P311 is highly expressed in skin hypertrophic scars. In this study, P311 over-expression was detected in a subset of tubular epithelial cells in clinical biopsy specimens of renal fibrosis; this over-expression, was found concurrent with α-smooth muscle actin (α-SMA) and transforming growth factor beta1 (TGFβ1) expression. Subsequently, these results were verified in a mouse experimental renal fibrosis model induced by unilateral ureteral obstruction. The interstitial deposition of collagen, α-SMA and TGF-β1 expression, and macrophage infiltration were dramatically decreased when P311 was knocked out. Moreover, TGFβ/Smad signaling had a critical effect on the promotion of renal fibrosis by P311. In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.

No MeSH data available.


Related in: MedlinePlus