Subhash Datta

University of Michigan, Ann Arbor, Michigan, United States

Are you Subhash Datta?

Claim your profile

Publications (4)30.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Human skin, like all other organs, undergoes chronological aging. In addition, unlike other organs, skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmental damage. The primary environmental factor that causes human skin aging is UV irradiation from the sun. This sun-induced skin aging (photoaging), like chronological aging, is a cumulative process. However, unlike chronological aging, which depends on the passage of time per se, photoaging depends primarily on the degree of sun exposure and skin pigment. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. This emerging information reveals that chronological aging and photoaging share fundamental molecular pathways. These new insights regarding convergence of the molecular basis of chronological aging and photoaging provide exciting new opportunities for the development of new anti-aging therapies. This article reviews our current understanding and presents new data about the molecular pathways that mediate skin damage by UV irradiation and by the passage of time.
    Archives of Dermatology 12/2002; 138(11):1462-70. DOI:10.1001/archderm.138.11.1462 · 4.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Humans express three distinct collagenases, MMP-1, MMP-8, and MMP-13, that initiate degradation of fibrillar type I collagen. We have previously reported that ultraviolet irradiation causes increased expression of MMP-1, but not MMP-13, in keratinocytes and fibroblasts in human skin in vivo. We report here that ultraviolet irradiation increases expression of MMP-8 in human skin in vivo. Western analysis revealed that levels of the full-length, 85 kDa proenzyme form of MMP-8 increased significantly within 8 h post ultraviolet irradiation (2 minimal erythema doses). Increased full-length MMP-8 protein was associated with infiltration into the skin of neutrophils, which are the major cell type that expresses MMP-8. Immunofluorescence revealed coexpression of MMP-8 and neutrophil elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression was not detected in nonirradiated or ultraviolet-irradiated human skin, indicating that increased MMP-8 following ultraviolet irradiation resulted from preexisting MMP-8 protein in infiltrating neutrophils. Pretreatment of skin with the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil infiltration. In contrast, all-trans retinoic acid and clobetasol were equally effective in blocking ultraviolet induction of MMP-1 and degradation of collagen in human skin in vivo. Taken together, these data demonstrate that ultraviolet irradiation increases MMP-8 protein, which exists predominantly in a latent form within neutrophils, in human skin in vivo. Although ultraviolet irradiation induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is initiated primarily by MMP-1, with little, if any, contribution by MMP-8.
    Journal of Investigative Dermatology 09/2001; 117(2):219-26. DOI:10.1046/j.0022-202x.2001.01432.x · 6.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by UV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.
    Journal of Clinical Investigation 10/2000; 106(5):663-70. DOI:10.1172/JCI9362 · 13.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transcription of the hCRABPII gene is retinoid inducible in human skin keratinocytes (KC) but, surprisingly, not in cultured cells. The promoter for the gene harbors three putative nuclear receptor binding sites: DR5, upstream of the transcription start site; DR1 (DR1d), distal to the site; and DR1 (DR1p), a proximal variant. DR1d, but not DR1p, is conserved between human and mouse. Although DR5 has been found to be a retinoid receptor target in COS-1 cells, the function of DR1 remains unknown. We examined the functions of these DR in retinoid regulation of the hCRABPII promoter in human KC. In reporter gene assays, no significant retinoid response was observed in the promoter in cultured KC; however, overexpression of retinoid receptor heterodimers RARgamma x RXRalpha restored the response. Gel supershift assays showed that endogenous RARgamma x RXRalpha levels are much lower in cultured KC than in skin in vivo. Ligand-binding assays showed that cultured KC contain only one-third of the level of retinoic acid receptor (RAR) and one-eighth of the level of retinoid X receptor found in KC in skin. Deletion of the DR1d or DR5 sites reduced retinoid-induced promoter activity by 63% and 27%, respectively. Isolated DR1d and DR5 sites, but not DR1p, efficiently bound RARgamma-RXRalpha and conferred RAR-selective retinoid responsiveness on a heterologous promoter. These data indicate that: (i) the previously reported lack of retinoid regulation of endogenous hCRABPII gene transcription in cultured KC is likely due to insufficient levels of RARgamma x RXRalpha, but not their cofactors; (ii) the conserved DR1d site is the major functional target in RARgamma x RXRalpha regulation of hCRABPII in KC; (iii) the DR1p site is nonfunctional due to its lack of affinity for RARgamma x RXRalpha, although its half-sites share high sequence homology with the consensus retinoid receptor-binding half-site.
    Journal of Investigative Dermatology 01/1999; 111(6):1109-15. DOI:10.1046/j.1523-1747.1998.00455.x · 6.37 Impact Factor