The role of FHL2 in wound healing and inflammation

Abstract

The 4‐and‐a‐half LIM domain protein 2 (FHL2) is a multifunctional adaptor protein that can interact with cell surface receptors, cytosolic adaptor and structural proteins, kinases, and nuclear transcription factors. It is involved in numerous functional activities, including the epithelial‐mesenchymal transition, cell proliferation, apoptosis, adhesion, migration, structural stability, and gene expression. Despite this, FHL2‐knockout (KO) mice are viable and fertile with no obvious abnormalities, rather suggesting a high capacity for fine‐tuning adjustment and functional redundancy of FHL2. Indeed, challenging FHL2‐KO cells or mice provided numerous evidences for the great functional significance of FHL2. In recent years, several reviews have been published describing the high capacity of FHL2 to bind diverse proteins as well as the versatile functions of FHL2, emphasizing in particular its role in cardiovascular diseases and carcinogenesis. Here, we view the function of FHL2 from a different perspective. We summarize the published data demonstrating the impact of FHL2 on wound healing and inflammation. FHL2 seems to be involved in numerous steps of these extremely complex and multidirectional but tightly regulated tissue remodeling processes, supporting tissue repair and coordinating inflammation. Deficiency of FHL2 not only slows down ongoing wound healing but also often turns it into a chronic condition.—Wixler, V. The role of FHL2 in wound healing and inflammation. FASEB J. 33, 7799–7809 (2019). http://www.fasebj.org

Four-And-A-Half LIM-Domain Protein 2 (FHL2) Deficiency Aggravates Cholestatic Liver Injury

“…Despite the effect on bone density, the Fhl2-ko mice have shown no obvious abnormalities, suggesting a high capacity for the fine-tuning adjustment and functional redundancy of Fhl2 under physiological conditions [9]. Additionally, here and as already described in previous studies [19], the Fhl2-ko control or sham-operated mice did not show any hepatologic abnormalities, and after BDL, a macroscopic analysis did not show pathological alterations besides the liver (data not shown).…”

“…FHL2 is ubiquitously expressed, but it exerts tissue-and cell context-specific functions that are often opposing. For example, FHL2 inhibits the migration of dendritic cells, but it induces the migration of fibroblasts [9]. FHL2 has also been shown to affect different steps of wound healing [9].…”

“…For example, FHL2 inhibits the migration of dendritic cells, but it induces the migration of fibroblasts [9]. FHL2 has also been shown to affect different steps of wound healing [9]. The deletion of the Fhl2 gene in mice has been found to result in impaired wound healing in the skin, the intestine or ischemic muscle tissues [10][11][12][13].…”

Detoxification, Hydrogen Sulphide Metabolism and Wound Healing Are the Main Functions That Differentiate Caecum Protein Expression from Ileum of Week-Old Chicken

“…An additional set of caecum-specific proteins associated with epithelium integrity was involved in cell migration and coordinated epithelial sheet motility. These included AHNAK, CAPZA2, CAPZA1, RDX, CTTN and FHL2 [ 40 , 41 , 42 , 43 , 44 , 45 ]. Furthermore, TNX, ENO2, and CHGA are exclusively expressed by neuronal and neuroendocrine cells [ 46 , 47 ], and their higher abundance in the caecum reflects differences in innervation as well as in the neuroendocrine cell distribution between small and large intestine observed earlier [ 48 ].…”

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

“…FHL2 has been detected in kidney podocytes where it interacts with and activates the Wnt/β-catenin signaling pathway [37]. Intriguingly, though FHL2 is not highly expressed in either spleen or immune cells, it is found to regulate inflammation in stressed or injured tissues [38,39]. Atherosclerosis, which may be considered a chronic inflammation of the vessel wall, was studied in FHL2-KO mice; these developed smaller atherosclerotic plaques after a cholesterol-enriched diet.…”