FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family

Abstract

Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine‐rich secreted protein, FIZZ1 (found in inflammatory zone). Murine (m) FIZZ1 is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium and white adipose tissue, and two related human genes. In control mice, FIZZ1 mRNA and protein expression occur at low levels in a subset of bronchial epithelial cells and in non‐neuronal cells adjacent to neurovascular bundles in the peribronchial stroma, and in the wall of the large and small bowel. During allergic pulmonary inflammation, mFIZZ1 expression markedly increases in hypertrophic, hyperplastic bronchial epithelium and appears in type II alveolar pneumocytes. In vitro, recombinant mFIZZ1 inhibits the nerve growth factor (NGF)‐mediated survival of rat embryonic day 14 dorsal root ganglion (DRG) neurons and NGF‐induced CGRP gene expression in adult rat DRG neurons. In vivo, FIZZ1 may modulate the function of neurons innervating the bronchial tree, thereby altering the local tissue response to allergic pulmonary inflammation.

Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance

“…A third group initially found resistin, which they named 'FIZZ3', as an expressed sequence tag related to a protein they found to be induced during lung inflammation known as 'found in inflammatory zone 1'. 58 Resistin is a 12.5 kDa cysteine-rich, C-terminal protein, whose mRNA expression has been predominantly observed in white adipose tissue, and to a lesser extent in the hypothalamus, the pituitary, BAT, the stomach, the large intestine, the adrenal gland and skeletal muscles, in rats. [59][60][61] In vitro studies showed that resistin is induced during adipocyte differentiation 53,57,62 and, as suggested by its signal sequence, is secreted into the media.…”

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

“…Resistin is a cysteine-rich secretory polypeptide expressed in adipocytes and belongs to a protein family called resistinlike molecules, which is also known as the found-in-inflammatory-zone family [1][2][3]. Resistin has been proposed as a potential link between obesity and insulin resistance.…”

The interplay between nutrients and the adipose tissue

“…The expression of resistin increases with increasing mass of adipose tissue. The resistin gene is identical to the FIZZ3 gene discovered earlier by Holcomb et al (2000). Although there are several observations that are compatible with a role for resistin in the development of insulin resistance in rodents as well as in man, there are data that support the notion that the major function of resistin in man may be related to inflammation (Weisberg et al 2003).…”

“…Although there are several observations that are compatible with a role for resistin in the development of insulin resistance in rodents as well as in man, there are data that support the notion that the major function of resistin in man may be related to inflammation (Weisberg et al 2003). Resistin like other RELM proteins comprises 105-114 amino acids and is characterized by a specific pattern made up of ten cysteine residues (Holcomb et al 2000). It circulates in the plasma as a trimer or a hexamer (Patel et al 2004).…”

“…Only two genes of the RELM family have been identified in the human genome that share homology with their mouse and rat counterparts: resistin, which is also known as RETN; RELMb, which is also termed RETNLB (Holcomb et al 2000;Weisberg et al 2003). In contrast to findings in mice, the human resistin gene has its highest expression in bone marrow, whereas expression in adipose tissue is much lower than that in mouse adipose tissue (Patel et al 2003).…”