Different Gene Expression Patterns in Human Papillary and Reticular Fibroblasts

Abstract

The dermis contains two distinct layers: the papillary and the reticular layers. In vitro cultures of the fibroblasts from these layers show that they are different. However, no molecular markers to differentiate between the two subtypes of fibroblasts are known. We performed gene expression analysis on cultured fibroblasts isolated from the papillary and reticular dermis. In all, 116 genes were found to be expressed differentially. Of these, 13 were validated by quantitative reverse transcriptase-PCR analysis and two markers could be validated at the protein level in monolayer cultures. Three markers showed differential expression in in vivo skin sections. The identified, characteristic markers of the two fibroblast subpopulations provide useful tools to perform functional studies on reticular and papillary fibroblasts.

Fibroblast-Endothelial Partners for Vascularization Strategies in Tissue Engineering

“…In addition, a recent work has shown that papillary fibroblasts can differentiate into reticular fibroblasts when cultured over several passages. 39 Also, a noteworthy aspect is that the same authors have attributed a higher expression of a-SMA to reticular fibroblasts, 23,39 whereas in the populations described here higher levels of this marker were found to be expressed by HDF. Moreover, although there is no evidence of PDPN functions in angiogenesis, TG2, in turn, has been described as a partner of endostatin, an antiangiogenic peptide present in the ECM close to ECs.…”

“…23 PDPN is a mucin-like transmembrane glycoprotein that has been associated to lymphangiogenesis 37 and is strongly expressed by papillary fibroblasts. Although no studies relating PDPN to angiogenesis during tissue regeneration are available, different patterns of the expression of PDPN, and TG2 and a-SMA, were found herein.…”

“…20,21 Considering their location within the dermis, fibroblasts are divided into papillary (superficial dermis) and reticular (deep dermis), exhibiting different characteristics in terms of cell morphology, production of ECM and growth factors, among others. 22,23 Although no specific markers distinguish both types of fibroblasts, differences in gene expression patterns exist, with reticular fibroblasts exhibiting an increased expression of genes involved in cell motility and contraction, including calponin-1 and transglutaminase-2 (TG2), whereas papillary fibroblasts characteristically express genes involved in the immune response, such as netrin-1 and podoplanin (PDPN). 23 Regarding vascularization, papillary fibroblasts seem to support the formation of highly branched tubular structures in vitro, while reticular fibroblasts do not.…”

“…22,23 Although no specific markers distinguish both types of fibroblasts, differences in gene expression patterns exist, with reticular fibroblasts exhibiting an increased expression of genes involved in cell motility and contraction, including calponin-1 and transglutaminase-2 (TG2), whereas papillary fibroblasts characteristically express genes involved in the immune response, such as netrin-1 and podoplanin (PDPN). 23 Regarding vascularization, papillary fibroblasts seem to support the formation of highly branched tubular structures in vitro, while reticular fibroblasts do not. 24 Understanding this process remains a challenge, since fibroblasts have the capacity to alter the mechanical extracellular microenvironment, thereby regulating vascularization processes.…”

Fibroblast heterogeneity: implications for human disease

“…Microarray analysis of cultured fibroblasts derived from mechanically separated dermis has revealed differences in gene expression (47); however, subsequent studies have yet to reproduce proposed markers of papillary and reticular layers. Dermatome experiments of this nature are inherently limited, since the level of sectioning cannot be precisely controlled, and therefore the possibility that reticular fibroblasts are included in the papillary sample cannot be excluded.…”