Heparanase 1: a key participant of inner root sheath differentiation program and hair follicle homeostasis

Abstract

Heparanase is a heparan sulphate endo-glycosidase which was previously detected in the outer root sheath of murine hair follicles. Heparanase overexpression was reported to improve mouse hair (re)growth. In this study, we investigated its involvement in human hair biology. Immunofluorescence detection was used to explore heparanase distribution in both anagen and catagen hair follicles. Heparanase functionality was assessed in in vitro cultured hair follicles, in the presence of a heparanase activity inhibitor. Our results showed that heparanase expression was (i) primarily located in the inner root sheath (IRS) of human hair follicle, and there (ii) restricted to anagen phase. Furthermore, inhibition of heparanase in in vitro cultured hair follicles induced a catagen-like process. Hair shaft retreat upward was accompanied by a decrease in Ki67-positive cells, the formation of an epithelial strand as evidenced by K14 keratin expression, and the loss of IRS as assessed by transglutaminase 1 and desmoglein labelling. IRS distribution of heparanase and the induction of catagen-like involution of hair follicles when a potent heparanase inhibitor is added suggest that heparanase is a key actor of IRS differentiation and hair homeostasis.

Heparan Sulfate Regulates Hair Follicle and Sebaceous Gland Morphogenesis and Homeostasis

“…Our findings are in accordance with the absence of HS impeding progression into catagen. Moreover, Malgouries et al (29) showed previously that there is an increase in heparanase expression in human anagen hair follicles; however, at the onset of catagen, hair follicle heparanase expression ceases, further supporting our findings. Therefore, our results clearly reveal the importance of fluctuations in the HS levels of hair follicle epithelial cells, which dictate hair follicle cycling and thus play a vital role in hair follicle homeostasis.…”

“…Previous studies have shown that heparanase expression varies throughout hair follicle cycling with increased expression in anagen hair follicles and decreased expression in catagen follicles (28). Moreover, the overexpression of heparanase accelerates the rate of anagen, and the authors speculate that the release of growth factors upon heparanase cleavage would play a major role (29). Herein we show that it is the absence of HS within the hair follicle that triggers the enhanced rate of anagen and not the release of growth factors upon heparanase digestion.…”

Hyperpigmentation in human solar lentigo is promoted by heparanase-induced loss of heparan sulfate chains at the dermal–epidermal junction

“…In normal tissue, heparanase is expressed in placenta, keratinocytes and platelets, but not in connective tissue cells [28][29][30][31]. In normal skin, heparanase is expressed in stratum corneum and hair inner root sheath, and may be involved in differentiation, desquamation and hair growth [30,31].…”

Heparanase Localization during Palatogenesis in Mice

“…Furthermore, heparanase expression is not restricted to pathological conditions and the activity has been found in hair follicle [26, 27] and in the skin [28]. Heparanase was detected in the outer root sheath of murine hair follicle [26], while it mainly expressed in the inner root sheath of human hair follicle [27], suggesting, despite of differential expression between the species, that heparanase may be a key factor in differentiation of a follicular stem cell and hair homeostasis.…”

“…Heparanase was detected in the outer root sheath of murine hair follicle [26], while it mainly expressed in the inner root sheath of human hair follicle [27], suggesting, despite of differential expression between the species, that heparanase may be a key factor in differentiation of a follicular stem cell and hair homeostasis. In human epidermis, heparanase expression has been reported to be closely related to keratinocyte differentiation and was mainly found in the stratum granulosum [28].…”