Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans

Madhusudan Grover, C. E. Bernard, P. J. Pasricha, H. P. Parkman, T. L. Abell, L. A. Nguyen, W. Snape, K. R. Shen, M. Sarr, J. Swain, M. Kendrick, S. Gibbons, Tamas Ordog, Gianrico Farrugia

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.

Original languageEnglish (US)
Pages (from-to)844-852
Number of pages9
JournalNeurogastroenterology and Motility
Volume24
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Gastroparesis
Platelet-Derived Growth Factor Receptors
Fibroblasts
Interstitial Cells of Cajal
Stomach
Staining and Labeling
Calcium-Activated Potassium Channels
Myenteric Plexus
Muscles
Ganglia

Keywords

  • Enteric nervous system
  • Fibroblast-like cells
  • Gastroparesis
  • Interstitial cells of Cajal
  • Platelet-derived growth factor receptor
  • Smooth muscle

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans. / Grover, Madhusudan; Bernard, C. E.; Pasricha, P. J.; Parkman, H. P.; Abell, T. L.; Nguyen, L. A.; Snape, W.; Shen, K. R.; Sarr, M.; Swain, J.; Kendrick, M.; Gibbons, S.; Ordog, Tamas; Farrugia, Gianrico.

In: Neurogastroenterology and Motility, Vol. 24, No. 9, 09.2012, p. 844-852.

Research output: Contribution to journalArticle

Grover, M, Bernard, CE, Pasricha, PJ, Parkman, HP, Abell, TL, Nguyen, LA, Snape, W, Shen, KR, Sarr, M, Swain, J, Kendrick, M, Gibbons, S, Ordog, T & Farrugia, G 2012, 'Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans', Neurogastroenterology and Motility, vol. 24, no. 9, pp. 844-852. https://doi.org/10.1111/j.1365-2982.2012.01944.x
Grover, Madhusudan ; Bernard, C. E. ; Pasricha, P. J. ; Parkman, H. P. ; Abell, T. L. ; Nguyen, L. A. ; Snape, W. ; Shen, K. R. ; Sarr, M. ; Swain, J. ; Kendrick, M. ; Gibbons, S. ; Ordog, Tamas ; Farrugia, Gianrico. / Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans. In: Neurogastroenterology and Motility. 2012 ; Vol. 24, No. 9. pp. 844-852.
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abstract = "Background Emerging evidence suggests that {"}fibroblast-like cells{"} (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.",
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T1 - Platelet-derived growth factor receptor α (PDGFRα)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans

AU - Grover, Madhusudan

AU - Bernard, C. E.

AU - Pasricha, P. J.

AU - Parkman, H. P.

AU - Abell, T. L.

AU - Nguyen, L. A.

AU - Snape, W.

AU - Shen, K. R.

AU - Sarr, M.

AU - Swain, J.

AU - Kendrick, M.

AU - Gibbons, S.

AU - Ordog, Tamas

AU - Farrugia, Gianrico

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N2 - Background Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.

AB - Background Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.

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KW - Fibroblast-like cells

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KW - Interstitial cells of Cajal

KW - Platelet-derived growth factor receptor

KW - Smooth muscle

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