-Recently, the role of Basement membrane (BM) proteins in the pathology of psoriasis has been increasingly reported
-McFadden et al. focused on streptococcal pharyngitis which can trigger self-limiting guttate psoriasis and hypothesized that streptokinase which is produced by streptococci can initiate lysis and disruption of BM, laminin. This can then promote keratinocyte instability and proliferative tendency; which are features of psoriasis
What is the basement membrane ?
-The basal membrane is a thin structure lying between the dermis and epidermis.
-It is composed of the fusion of two layers, the basal lamina (of epidermal origin) and the underlying layer of reticular connective tissue (dermal origin).
-In terms of molecular structure it includes laminin, collagen (type III, IV and VII) and hemidesmosomes. The latter are attached to the epidermal stem cells of the basal layer.
-It is essential for for the epidermal structure to stick tightly to the rest of the skin. It is itself firmly in contact to the dermis with anchoring fibrils (collagen 7) and Surface adhesion molecules (SAM).
-The basement membrane is not normally visible under optical microscopy except in pathological states (such as systemic lupus erythematosus). It is always visible under electron microscopy.
It is difficult to image its plane structure when seen in conventional sections perpendicular to the skin.
However it is a plane and separates the epidermis from the dermis.
-It is permeable and can therefore act as a barrier and filter passage of nutrients, inflammatory signals…between the two components of the skin.
-It prevents malignant cells from entering the dermis (In Situ vs invasive cancers)
-It is also essential for angiogenesis (development of new blood vessels). Basement membrane proteins have been found to accelerate differentiation of endothelial cells.
As you know, the epidermis is NOT vascularized which means that inflammatory cells such as lymphocytes and histiocytes need to leave the blood stream to reach the dermis (margination, rolling, diapedesis). Only then do they release cytokines (such as Tumor Necrosis Factor (TNF)). These cytokines then migrate to the epidermis which lead to reduced keratinocyte differentiation and increased turnover. (CAM and integrins ?)
The following from Osaka, Japan study seeks to identify the role of the basement membrane in psoriasis.
After examining the expression of BM proteins (in IMQ-induced psoriasis mouse model), it was found that:
-increased expression of laminin-alpha5, gamma1 and beta1 integrin (which binds laminin 511) along the BM and basolateral surface of basal keratinocytes
–laminin 511 increases HaCaT cell proliferation and reduces apoptosis (HaCaT cells are a sort of immortal keratinocytes highly capable to differentiate: click HERE to read more)
-laminin 332 and beta 4 integrin (which binds laminin 332) were also increased along the BM
This study highlights a neglected aspect of psoriasis physiopathology…and introduces a potential target in the treatment of psoriasis
Dr Christophe HSU – dermatologist. Geneva, Switzerland
Source of information: P03-09 [O3-34] Natsumi A et al. The role of basement membrane components on psoriasis in mice. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2015 – Okayama, Japan