Transforming growth factor-β signaling pathway in Marfan's syndrome: a preliminary histopathological study

Marfan's syndrome is an inherited disorder that affects the connective tissue. It has been proposed that mutations of FBN1 gene or of transforming growth factor (TGF)-beta type II receptor may be responsible for its pathogenesis. However, the role of TGF-beta signaling pathway in the development of Marfan's syndrome has not been comprehensively investigated.

Surgical specimens of the aorta were obtained from two female Marfan patients, and the control aortic tissue was taken from an autopsy of a healthy individual. The aortic specimens were examined with hematoxylin-eosin, Masson's trichrome, von Gieson/victoria blue-van Gieson bichrome, and immunohistochemical stainings of TGF-beta1, TGF-beta type I receptor, Smad2/3, Smad4 and Smad7.

Hematoxylin-eosin staining demonstrated severe elastic lamellar disruption and patchy vascular smooth muscle dissolution in the aortic media of the Marfan patients. Collagen deposition, interlamilar elastic fiber fragmentation, loss or proliferation, and acid mucopolysaccharide accumulation were observed in the disarrayed aortic wall structures of Marfan patients by Masson's trichrome, victoria blue-van Gieson bichrome, and Alcian blue and periodic schiff's (AB-PAS) stainings, respectively. By immunohistochemistry, structural disruptions with enhanced TGF-beta;1 in the cytoplasm, Smad2/3 in the interstices, Smad4 in the cytoplasm, nuclei or interstices, and OOO Smad7, in the nucleus along with attenuated TGF-beta type I receptor in the aortic tissues of Marfan patients in comparison to the healthy control.

Marfan patients may have aberrant TGF-beta signaling pathway associated with increased collagen deposition, interlamilar elastic fiber degenerative changes, and acid mucopolysaccharide accumulation. The signaling dysregulation may play an important role in the pathogenesis of this genetic disorder.