# Chronic Exposure of Renal Progenitor Cells (HRTPT) to As (III) Implicates Microfibril Associated Protein 5 (MFAP5) in the Activation of Carcinoembryonic Antigen Related Cell Adhesion Molecules (CEACAM 5 and 6)

**Authors:** Md Ehsanul Haque, Donald A. Sens, Scott H. Garrett

PMC · DOI: 10.3390/cimb47060455 · Current Issues in Molecular Biology · 2025-06-12

## TL;DR

Chronic exposure to arsenic in kidney cells leads to changes in proteins like MFAP5 and CEACAM 5/6, which may contribute to kidney disease and cancer.

## Contribution

The study identifies MFAP5 and CEACAM 5/6 as potential therapeutic targets in arsenic-induced kidney disease.

## Key findings

- Chronic arsenic exposure increases MFAP5 and CEACAM 5/6 in renal cells.
- Arsenic exposure activates pAKT/AKT and SOX9 pathways in kidney cells.
- MFAP5 and CEACAM 5/6 may serve as therapeutic targets for CKD.

## Abstract

Studies on populations exposed to inorganic arsenic (iAs) have shown an association with the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to the long-term alterations that might lead to CKD or RCC. This laboratory’s hypothesis is that renal exposure to iAs might alter the renal cells responsible for the repair and regeneration of nephrons damaged by iAs exposure or other renal toxicants. The kidney possesses a minority epithelial cell population that co-expresses PROM1 and CD24, which are believed to be involved in renal epithelial cell repair. The purpose of this work is to understand the pathogenesis of CKD in renal cortical epithelial cells. Our model consists of acute and chronic exposure of i-As (III) to “Human Renal Tubular Precursor TERT” (HRTPT). The microarray and gene validation study demonstrated a sudden induction of microfibril associated protein 5 (MFAP5) and carcinoembryonic antigen related cell adhesion molecule 5 and 6 (CEACAM 5 and 6) in chronic i-As (III)-exposed cells. Chronically exposed cells also exhibited an induction of the pAKT/AKT pathway and SOX9 transcription factor. The targeting of MFAP5 and CEACAM 5/6 could, therefore, provide a potential therapeutic approach to CKD.

## Linked entities

- **Genes:** MFAP5 (microfibril associated protein 5) [NCBI Gene 8076], CEACAM5 (CEA cell adhesion molecule 5) [NCBI Gene 1048], CEACAM6 (CEA cell adhesion molecule 6) [NCBI Gene 4680], PROM1 (prominin 1) [NCBI Gene 8842], CD24 (CD24 molecule) [NCBI Gene 100133941], SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662]
- **Proteins:** MFAP5 (microfibril associated protein 5), CEACAM5 (CEA cell adhesion molecule 5), CEACAM6 (CEA cell adhesion molecule 6), Akt (Akt kinase), AKT1 (AKT serine/threonine kinase 1)
- **Chemicals:** iAs (PubChem CID 78017)
- **Diseases:** chronic kidney disease (MONDO:0005300), renal cell carcinoma (MONDO:0005086)

## Full-text entities

- **Genes:** TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, CD24 (CD24 molecule) [NCBI Gene 100133941] {aka CD24A}, MFAP5 (microfibril associated protein 5) [NCBI Gene 8076] {aka AAT9, MAGP-2, MAGP2, MFAP-5, MP25}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** RCC (MESH:D002292), CKD (MESH:D051436)
- **Chemicals:** As (III (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12191821/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12191821/full.md

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Source: https://tomesphere.com/paper/PMC12191821