Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.
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.
