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Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.

Publication ,  Journal Article
Schmitz, JC; Protiva, P; Gattu, AK; Utsumi, T; Iwakiri, Y; Neto, AG; Quinn, M; Cornwell, ML; Fitchev, P; Lugea, A; Crawford, SE; Chung, C
Published in: Am J Pathol
December 2011

Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive cerulein-induced (50 μg/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, α-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-β1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wild-type pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wild-type mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wild-type mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in pancreatitis.

Duke Scholars

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

December 2011

Volume

179

Issue

6

Start / End Page

2990 / 2999

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Thrombospondin 1
  • Serpins
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Pathology
  • Pancreatitis
  • Pancreas
  • Nerve Growth Factors
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schmitz, J. C., Protiva, P., Gattu, A. K., Utsumi, T., Iwakiri, Y., Neto, A. G., … Chung, C. (2011). Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1. Am J Pathol, 179(6), 2990–2999. https://doi.org/10.1016/j.ajpath.2011.08.009
Schmitz, John C., Petr Protiva, Arijeet K. Gattu, Teruo Utsumi, Yasuko Iwakiri, Antonio G. Neto, Margo Quinn, et al. “Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.Am J Pathol 179, no. 6 (December 2011): 2990–99. https://doi.org/10.1016/j.ajpath.2011.08.009.
Schmitz JC, Protiva P, Gattu AK, Utsumi T, Iwakiri Y, Neto AG, et al. Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1. Am J Pathol. 2011 Dec;179(6):2990–9.
Schmitz, John C., et al. “Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.Am J Pathol, vol. 179, no. 6, Dec. 2011, pp. 2990–99. Pubmed, doi:10.1016/j.ajpath.2011.08.009.
Schmitz JC, Protiva P, Gattu AK, Utsumi T, Iwakiri Y, Neto AG, Quinn M, Cornwell ML, Fitchev P, Lugea A, Crawford SE, Chung C. Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1. Am J Pathol. 2011 Dec;179(6):2990–2999.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

December 2011

Volume

179

Issue

6

Start / End Page

2990 / 2999

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Thrombospondin 1
  • Serpins
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Pathology
  • Pancreatitis
  • Pancreas
  • Nerve Growth Factors
  • Mice, Inbred C57BL