Limits...
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

Increased levels and cellular localization of P311 in mouse renal fibrosis.(A) P311 expression and distribution in kidney tissues after sham-operation (Sham) or unilateral ureteral obstruction (UUO) in adult mice, as evidenced by immunohistochemistry. Black arrowhead indicates the P311-positive region. P311-positive region was quantified in stained sections from the Sham (n = 6) and UUO (n = 6) groups. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01. (B) TGFβ1 and α-SMA as well as acidophilic degeneration seem to be co-localized with P311 in some tubular epithelial cells within serial sections from mouse obstructed kidneys (n = 6). (a) Hematoxylin and eosin staining of mouse renal fibrosis samples (n = 6). Black arrowhead indicates acidophilic degeneration. (b) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the P311-positive region. (c) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the α-SMA-positive region. (d) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the TGFβ1-positive region. (e) Negative control for the immunohistochemical staining on mouse renal fibrosis samples (n = 6). (A,B) are representative of at least three similar experiments. Scale bar: 100μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663757&req=5

f2: Increased levels and cellular localization of P311 in mouse renal fibrosis.(A) P311 expression and distribution in kidney tissues after sham-operation (Sham) or unilateral ureteral obstruction (UUO) in adult mice, as evidenced by immunohistochemistry. Black arrowhead indicates the P311-positive region. P311-positive region was quantified in stained sections from the Sham (n = 6) and UUO (n = 6) groups. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01. (B) TGFβ1 and α-SMA as well as acidophilic degeneration seem to be co-localized with P311 in some tubular epithelial cells within serial sections from mouse obstructed kidneys (n = 6). (a) Hematoxylin and eosin staining of mouse renal fibrosis samples (n = 6). Black arrowhead indicates acidophilic degeneration. (b) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the P311-positive region. (c) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the α-SMA-positive region. (d) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the TGFβ1-positive region. (e) Negative control for the immunohistochemical staining on mouse renal fibrosis samples (n = 6). (A,B) are representative of at least three similar experiments. Scale bar: 100μm.

Mentions: To determine whether the increased P311, TGF-β1 and α-SMA levels in renal fibrosis in humans were also present in mice, we induced renal interstitial fibrosis by unilateral ureteral obstruction (UUO). HE staining revealed marked tubular dilation and atrophy, interstitial matrix deposition and inflammatory cell infiltration 7 days after UUO. Meanwhile, some tubular epithelial cells in obstructed kidneys became swollen and exhibited acidophilic degeneration (data not shown). To examine P311 localization, we performed immunohistochemistry with an antibody against P311. P311 was primarily localized to the cytoplasm of some tubular epithelial cells in P311+/+ mice after UUO. However, we did not detect P311 expression in tubular epithelial cells from mice in the sham operation (Sham) group (Fig. 2A, 15.42-fold difference, P < 0.001). We examined TGFβ1 and α-SMA expression in relation to P311 expression. The TGFβ1- and α-SMA-positive regions and the acidophilic degeneration regions seem to be co-localized with the P311-positive regions in some serial sections of tubular epithelial cells (Fig. 2B). Together, these data indicated that P311 expression increased and P311 seem be co-localized with TGFβ1 and α-SMA in obstructed kidneys in mice, which may contribute to the pathology of 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)

Increased levels and cellular localization of P311 in mouse renal fibrosis.(A) P311 expression and distribution in kidney tissues after sham-operation (Sham) or unilateral ureteral obstruction (UUO) in adult mice, as evidenced by immunohistochemistry. Black arrowhead indicates the P311-positive region. P311-positive region was quantified in stained sections from the Sham (n = 6) and UUO (n = 6) groups. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01. (B) TGFβ1 and α-SMA as well as acidophilic degeneration seem to be co-localized with P311 in some tubular epithelial cells within serial sections from mouse obstructed kidneys (n = 6). (a) Hematoxylin and eosin staining of mouse renal fibrosis samples (n = 6). Black arrowhead indicates acidophilic degeneration. (b) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the P311-positive region. (c) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the α-SMA-positive region. (d) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the TGFβ1-positive region. (e) Negative control for the immunohistochemical staining on mouse renal fibrosis samples (n = 6). (A,B) are representative of at least three similar experiments. Scale bar: 100μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Increased levels and cellular localization of P311 in mouse renal fibrosis.(A) P311 expression and distribution in kidney tissues after sham-operation (Sham) or unilateral ureteral obstruction (UUO) in adult mice, as evidenced by immunohistochemistry. Black arrowhead indicates the P311-positive region. P311-positive region was quantified in stained sections from the Sham (n = 6) and UUO (n = 6) groups. Data are presented as the mean ± SD. *P < 0.05; **P < 0.01. (B) TGFβ1 and α-SMA as well as acidophilic degeneration seem to be co-localized with P311 in some tubular epithelial cells within serial sections from mouse obstructed kidneys (n = 6). (a) Hematoxylin and eosin staining of mouse renal fibrosis samples (n = 6). Black arrowhead indicates acidophilic degeneration. (b) P311 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the P311-positive region. (c) α-SMA immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the α-SMA-positive region. (d) TGFβ1 immunoreactivity in the cytoplasm of some tubular epithelial cells from mouse renal fibrosis samples (n = 6). Black arrowhead indicates the TGFβ1-positive region. (e) Negative control for the immunohistochemical staining on mouse renal fibrosis samples (n = 6). (A,B) are representative of at least three similar experiments. Scale bar: 100μm.
Mentions: To determine whether the increased P311, TGF-β1 and α-SMA levels in renal fibrosis in humans were also present in mice, we induced renal interstitial fibrosis by unilateral ureteral obstruction (UUO). HE staining revealed marked tubular dilation and atrophy, interstitial matrix deposition and inflammatory cell infiltration 7 days after UUO. Meanwhile, some tubular epithelial cells in obstructed kidneys became swollen and exhibited acidophilic degeneration (data not shown). To examine P311 localization, we performed immunohistochemistry with an antibody against P311. P311 was primarily localized to the cytoplasm of some tubular epithelial cells in P311+/+ mice after UUO. However, we did not detect P311 expression in tubular epithelial cells from mice in the sham operation (Sham) group (Fig. 2A, 15.42-fold difference, P < 0.001). We examined TGFβ1 and α-SMA expression in relation to P311 expression. The TGFβ1- and α-SMA-positive regions and the acidophilic degeneration regions seem to be co-localized with the P311-positive regions in some serial sections of tubular epithelial cells (Fig. 2B). Together, these data indicated that P311 expression increased and P311 seem be co-localized with TGFβ1 and α-SMA in obstructed kidneys in mice, which may contribute to the pathology of 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