Confocal laser scanning analysis of the association of fibulin-2 with fibrillin-1 and fibronectin define different stages of skin regeneration

J Invest Dermatol. 1999 Jan;112(1):97-101. doi: 10.1046/j.1523-1747.1999.00483.x.


The fibulins represent a novel family of extracellular matrix proteins. We report the temporo-spatial expression of fibulin-2 in skin regenerating from keratinocyte autografts. In normal dermis, fibulin-2 was associated with the fibrillin-containing microfibrillar apparatus, except for the portion immediately adjacent to the dermo-epidermal junction. In contrast, early regenerating dermis showed numerous fusiform fibrillin-microfibrils along the basement membrane, whereas fibulin-2 was present in a distinct and separate layer below. Both proteins formed independent fibrillar systems also in the reticular dermis without significant colocalization; however, over time both fibril systems became congruent: after 4 mo there was extensive colocalization of fibulin-2/fibrillin in the reticular dermis, after 17 and 24 mo this also occurred in the papillary dermis. Simultaneous visualization of fibulin-2 and fibronectin revealed an inverse pattern: complete colocalization at 7 d and discordant distribution 17-24 mo after grafting. In particular, the fibrillar fibronectin pattern at early time points changed into a faint granular distribution throughout the dermis and along the subbasement membrane region as in normal skin. Dermal fibroblast cultures showed that fibrillin and fibronectin participated in distinct fibrillar systems; however, fibulin-2 colocalized with either protein. We propose that, in regenerating skin, fibulin-2 is a late component of the cutaneous microfibrillar apparatus with an earlier existence in a fibrillar matrix mediated by fibronectin. This suggests interaction of fibulin-2 with both fibronectin fibrils and fibrillin microfibrils, and is consistent with in vitro binding data.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Calcium-Binding Proteins / analysis*
  • Extracellular Matrix Proteins / analysis*
  • Fibrillin-1
  • Fibrillins
  • Fibronectins / analysis*
  • Humans
  • Microfilament Proteins / analysis*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Regeneration*
  • Skin / chemistry*


  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Fibronectins
  • Microfilament Proteins
  • fibulin 2