Kindlin-2 expression in adult tissues correlates with their embryonic origins

Abstract

Kindlin-2 functions in the maintenance of homeostasis and in human diseases. This study investigated the interrelationship between Kindlin-2 expression in tissues and the corresponding germ layers from which these tissues originated. Kindlin-2 expression was examined in normal adult human organs and human cancer tissues by immunohistochemical analyses. Analysis of Kindlin-2 mRNA levels in adult human organs in the Oncomine dataset revealed Kindlin-2 is highly expressed in mesoderm-derived organs. However, Kindlin-2 was negative or weakly expressed in endoderm/ectoderm-derived organs. Interestingly, the abnormal expression of Kindlin-2 was observed in a variety of human cancers. In agreement with its expression profile in humans, Kindlin-2 was also highly expressed in mesoderm-derived organs in mouse embryos with the exception of strong Kindlin-2 expression in ectoderm-derived spinal cord and ganglia, tissues that are highly mobile during embryonic development. Importantly, we demonstrated the expression level of Kindlin-2 in adult organs correlated with their embryonic dermal origins and deregulation of Kindlin-2 in tissues is associated with tumor progression. This finding will help us understand the dual role of Kindlin-2 in the regulation of tumor progression and embryonic development.

Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure

“…Although ubiquitously expressed 18 , Kindlin-2 is most abundantly expressed in cardiac and skeletal muscle 3, 16 . To investigate the potential role of Kindlin-2 in the mammalian heart, we generated CM-specific knockout (KO) mice by conditionally deleting Kindlin-2 in developing CMs at around embryonic day (E) 8.0, by crossing Kindlin-2 f/f mice 28 with the α-MHC-Cre mouse line 29 .…”

“…The Kindlin family consists of three isoforms (Kindlin-1, -2, and -3), which show tissue-specific expression patterns 14, 16, 18 . Only Kindlin-2, also known as Mig-2, is reported to be expressed in cardiac tissue 3, 16 .…”

Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm

“…Kindlin-1 was also highly expressed in endocrine cells, indicating that Kindlin-1 may play a role in endocrine function and related diseases which warrant further study. We previously reported that Kindlin-2 was highly expressed in mesoderm originated organs but weakly expressed in ectoderm/ endoderm originated organs [8]. In this study, we found that Kindlin-1 expression in human tissues is contrary to that of Kindlin-2.…”

“…However, the Kindlin-1 expression profile in the whole human body remains unknown. In comparison, we previously found that the Kindlin family protein Kindlin-2 is highly expressed in mesoderm-derived tissues [8]. Despite sequence homology between Kindlin-1 and Kindlin-2, some of their biological functions are different and they cannot functionally compensate to each other [9][10][11].…”

Kindlin-2 Modulates the Survival, Differentiation, and Migration of Induced Pluripotent Cell-Derived Mesenchymal Stromal Cells

“…Our data indicated that Kindlin-2 was expressed in BM-MSCs at significantly higher levels than the iPSCs that we used to differentiate iPSC-MSCs (Figure 1(a)). During embryonic development, Kindlin-2, which is weakly expressed in embryonic stem cells, begins to accumulate at increased levels in mesodermal-derived tissues [3, 30, 31]. Furthermore, the expression of Kindlin-2 increases as epithelial-shape embryonic stem cells proceed through epithelial-mesenchymal transition (EMT) towards mesodermal-differentiated cells [32].…”