Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes.

Abstract

The polypeptide composition of epidermal keratin varies in disease . To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies . The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes . Specifically, a 50-kilodalton (kd) (AEl-positive) and a 58-kd (AE3-positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes . A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology . A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para-or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a non hyperproliferative disease . These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis-specific and may represent markers for hyperproliferative keratinocytes in general . In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events . Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, diseasespecific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases.The keratins are a group of water-insoluble proteins (40-70 Kdaltons [kd])' that form 10-nm desmosome-associated tonofilaments in all epithelia (15,17,18,61,63,64). Four major keratins (50, 56.5, 58, and 65-67 kd) have been identified in normal human epidermis (7, 21, 40, 72; cf. 4, 49, 62); significant alterations in epidermal keratin composition can occur, however, as a result of disease (1,3,5,25,26,28,33,34,36,37,40,50,52,54,66,71) as well as changes in cellular growth environment (10,20,29,55,61,62 -67-kd keratins (1, 5, 8, 37, 50, 54, 66). In addition, Thaler et al. (65,66) reported that two water-insoluble proteins of -54 and 57 kd are unique to psoriatic scale, although Baden et al. (5) found no "psoriasis-specific" keratin changes . Hunter and Skerrow (26) reported that certain abnormal keratin polypeptides ranging from 55-63 kd (probably corresponding to 50-58 kd in our gel system) are present in the scales of psoriasis, atopic dermatitis, and seborrheic dermatitis, as well as in the stratum comeum oftape-stripped epidermis . Interestingly, Kubilus et al. (28) found that keratins of another disease, basal cell 13...

Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis

“…4B with D). In epidermal hyperplasia, loss or downregulation of K10 is accompanied by the induction of keratin K6, a keratin normally expressed in hair follicles but not in the interfollicular epidermis (Takahashi et al, 1998;Weiss et al, 1984). We found that in Rb F19/F19 ;K14cre mice, patches of cells showed overlap of K6 and K10 expression throughout the hyperplastic epidermis (Fig.…”

Epidermal differentiation: the bare essentials.

“…More recent studies with differentiating culture systems have revealed that at greatly elevated levels, TGF-/3s can influence biochemical markers of keratinization, but at these high levels, they inhibit rather than promote, K1, K10, and filaggrin expression (Ma~nsbridge and Hanawalt,..1988;Choi and Fuchs, 1990). At li|gh concentration, TGF-/~s also enhance expression of K6 (56 kD) and K16 (48 kD), keratins more commonly associated with suprabasal layers of epidermis undergoing (a) wound healing (Mansbridge and Knapp, 1987) and (b) hyperproliferation (Weiss et al, 1984;Stoler et al, 1988). Studies using floating epidermal cultures have shown that induction of K6 and K16 is accompanied by morphological changes typical of squamous cell carcinomas, including increased stratification, vacuolization, and coilocyte formation (Choi and Fuchs, 1990).…”

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

“…K6 is normally expressed in the outer root sheath of the hair follicles but not in the interfollicular epidermis (ref. 21; Fig. 2I).…”