Abstract
Although the transcription factor EGR1 is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions. A broad range of signals induce Egr1 gene expression via numerous regulatory elements identified in the Egr1 promoter. EGR1 is also the target of multiple post-translational modifications, which modulate EGR1 transcriptional activity. Despite the myriad regulators of Egr1 transcription and translation, and the numerous biological functions identified for EGR1, the literature reveals a recurring theme of EGR1 transcriptional activity in connective tissues, regulating genes related to the extracellular matrix. Egr1 is expressed in different connective tissues, such as tendon (a dense connective tissue), cartilage and bone (supportive connective tissues), and adipose tissue (a loose connective tissue). Egr1 is involved in the development, homeostasis, and healing processes of these tissues, mainly via the regulation of extracellular matrix. In addition, Egr1 is often involved in the abnormal production of extracellular matrix in fibrotic conditions, and Egr1 deletion is seen as a target for therapeutic strategies to fight fibrotic conditions. This generic EGR1 function in matrix regulation has little-explored implications but is potentially important for tendon repair.
Highlights
The transcription factor Early growth response gene 1 (EGR1) is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions
The dense connective tissues can be divided into two subtypes: (1) the regular connective tissue, which refers to tendons/ligaments built with regular collagen fibers and (2) the irregular connective tissues embedding organs, composed of irregular collagen fibers, such as skeletal muscle connective tissue, pericardium, or peritoneum
In addition to being involved in matrix production in normal conditions and fibrotic processes, EGR1 transcription factor has been associated with numerous cancers and has been shown to act as a tumor suppressor or a tumor promoter depending on cancer types, for reviews see [174,175]
Summary
Connective tissues support and link organs, and are composed of specialized fibroblasts derived from mesenchymal stem cells. The presence of type I collagen is not specific to tendon since it is expressed in many other connective tissues such as bone and adipose tissue. A multitude of matrix molecules are involved in collagen fibrillogenesis leading to the specific spatial organization of type I collagen in tendons, reviewed in [5,6]. In addition to SCX, two other transcription factors have been shown to positively regulate the expression of Col1a and Col1a2 genes and type I fibril organization in tendons: the homeobox Mohawk (MKX) and the zinc finger transcription factor Early growth response gene 1 (EGR1). We will focus on the EGR1 transcription factor and its generic function as a regulator of gene transcription of extracellular matrix components in tendon, bone, and adipose tissue (Figure 1), both in physiological and pathological conditions
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