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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

Interstitial collagen deposition and P311, α-SMA and TGFβ1 expression in human renal fibrosis.(A) Hematoxylin and eosin staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the remarkable tubular atrophy. (B) Masson trichrome staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the interstitial collagen fibril deposition. (C) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the P311-positive region. (D) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the α-SMA-positive region. (E) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the TGFβ1-positive region. (F) Negative control for the immunohistochemical staining on human renal fibrosis samples (n = 22). (G) Hematoxylin and eosin staining of healthy human kidney samples (n = 2). Black arrowhead indicates the normal renal tubules. (H) Masson trichrome staining of healthy human kidney samples (n = 2). Black arrowhead indicates the little interstitial collagen fibril. (I) P311 is negative in normal human renal tubular epithelial cells (n = 2). Scale bar: 100μm.
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f1: Interstitial collagen deposition and P311, α-SMA and TGFβ1 expression in human renal fibrosis.(A) Hematoxylin and eosin staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the remarkable tubular atrophy. (B) Masson trichrome staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the interstitial collagen fibril deposition. (C) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the P311-positive region. (D) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the α-SMA-positive region. (E) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the TGFβ1-positive region. (F) Negative control for the immunohistochemical staining on human renal fibrosis samples (n = 22). (G) Hematoxylin and eosin staining of healthy human kidney samples (n = 2). Black arrowhead indicates the normal renal tubules. (H) Masson trichrome staining of healthy human kidney samples (n = 2). Black arrowhead indicates the little interstitial collagen fibril. (I) P311 is negative in normal human renal tubular epithelial cells (n = 2). Scale bar: 100μm.

Mentions: We investigated 22 human clinical biopsy specimens of renal fibrosis and 2 normal human kidney tissue samples, which were diagnosed via histopathology (Table 1). Remarkable tubular dilation and atrophy, interstitial expansion and abundant inflammatory cell infiltration were observed after hematoxylin and eosin (HE) staining (Fig. 1A). Masson trichrome staining revealed a large amount of interstitial collagen fibril deposition (Fig. 1B). P311 protein levels were significantly increased in the cytoplasm of some tubular epithelial cells in human renal fibrosis tissues samples, as evidenced by immunohistochemical analysis (Fig. 1C). In addition, we examined α-SMA and TGF-β1 expression and found that both α-SMA and TGF-β1 were highly expressed in the cytoplasm of some tubular epithelial cells in human renal fibrosis tissues, and their expression pattern was similar to that of P311 (Fig. 1C–F). Normal human kidney tissue samples indicate the normal renal tubules and the little interstitial collagen fibril (Fig. 1G,H). However, tubular epithelial cells in normal human kidney tissues were negative for P311 (Fig. 1I); these cells were also negative for TGF-β1 and α-SMA (data not shown). These results indicated the possible role of P311 in human renal fibrogenesis.


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)

Interstitial collagen deposition and P311, α-SMA and TGFβ1 expression in human renal fibrosis.(A) Hematoxylin and eosin staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the remarkable tubular atrophy. (B) Masson trichrome staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the interstitial collagen fibril deposition. (C) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the P311-positive region. (D) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the α-SMA-positive region. (E) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the TGFβ1-positive region. (F) Negative control for the immunohistochemical staining on human renal fibrosis samples (n = 22). (G) Hematoxylin and eosin staining of healthy human kidney samples (n = 2). Black arrowhead indicates the normal renal tubules. (H) Masson trichrome staining of healthy human kidney samples (n = 2). Black arrowhead indicates the little interstitial collagen fibril. (I) P311 is negative in normal human renal tubular epithelial cells (n = 2). Scale bar: 100μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Interstitial collagen deposition and P311, α-SMA and TGFβ1 expression in human renal fibrosis.(A) Hematoxylin and eosin staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the remarkable tubular atrophy. (B) Masson trichrome staining of human renal fibrosis samples (n = 22). Black arrowhead indicates the interstitial collagen fibril deposition. (C) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the P311-positive region. (D) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the α-SMA-positive region. (E) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from human renal fibrosis samples (n = 22). Black arrowhead indicates the TGFβ1-positive region. (F) Negative control for the immunohistochemical staining on human renal fibrosis samples (n = 22). (G) Hematoxylin and eosin staining of healthy human kidney samples (n = 2). Black arrowhead indicates the normal renal tubules. (H) Masson trichrome staining of healthy human kidney samples (n = 2). Black arrowhead indicates the little interstitial collagen fibril. (I) P311 is negative in normal human renal tubular epithelial cells (n = 2). Scale bar: 100μm.
Mentions: We investigated 22 human clinical biopsy specimens of renal fibrosis and 2 normal human kidney tissue samples, which were diagnosed via histopathology (Table 1). Remarkable tubular dilation and atrophy, interstitial expansion and abundant inflammatory cell infiltration were observed after hematoxylin and eosin (HE) staining (Fig. 1A). Masson trichrome staining revealed a large amount of interstitial collagen fibril deposition (Fig. 1B). P311 protein levels were significantly increased in the cytoplasm of some tubular epithelial cells in human renal fibrosis tissues samples, as evidenced by immunohistochemical analysis (Fig. 1C). In addition, we examined α-SMA and TGF-β1 expression and found that both α-SMA and TGF-β1 were highly expressed in the cytoplasm of some tubular epithelial cells in human renal fibrosis tissues, and their expression pattern was similar to that of P311 (Fig. 1C–F). Normal human kidney tissue samples indicate the normal renal tubules and the little interstitial collagen fibril (Fig. 1G,H). However, tubular epithelial cells in normal human kidney tissues were negative for P311 (Fig. 1I); these cells were also negative for TGF-β1 and α-SMA (data not shown). These results indicated the possible role of P311 in human renal fibrogenesis.

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